Clobazam

Identification

Summary

Clobazam is a benzodiazepine used as adjunct treatment in seizures associated with Lennox-Gastaut syndrome.

Brand Names
Onfi, Sympazan
Generic Name
Clobazam
DrugBank Accession Number
DB00349
Background

Clobazam belongs to the 1,5-benzodiazepine class of drugs and is marketed under different names, Onfi, Frisium, Urbanyl, and others.9. Clobazam was first synthesized in 1966 and first published in 1969, following the incidental synthesis and discovery of the first benzodiazepine chlordiazepoxide in the 1950s.12 Unlike older 1,4-benzodiazepines, clobazam has a better side-effects profile, particularly less sedative and amnesic effects.15,9 This is likely because of clobazam's higher affinity to the α2 subunit of the GABAA receptor, which mediates anxiolytic effects, than the α1 subunit, which mediates sedative effect.9 Additionally, clobazam is believed to be a partial agonist to the GABAA receptor rather than non-selective full receptor agonists like 1,4-benzodiazepines, thus potentially explaining the decreased incidence of sedative effects.16,17

Clobazam has been marketed as an anxiolytic since 1975 and an anticonvulsant since 1984.1,2 In October 21, 2011, the FDA approved clobazam as an adjunctive treatment for seizures associated with Lennox-Gastaut syndrome in adults and children aged two years and older.14 In 2005, clobazam also received approval from Health Canada as an add-on therapy for generalized tonic-clonic, myoclonic, and focal impaired awareness seizures.18

Type
Small Molecule
Groups
Approved, Illicit
Structure
Weight
Average: 300.74
Monoisotopic: 300.066555377
Chemical Formula
C16H13ClN2O2
Synonyms
  • 1-phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-dioxo-3H-1,5-benzodiazepine
  • 7-Chloro-1-methyl-5-phenyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione
  • Clobazam
  • Clobazamum
External IDs
  • H 4723
  • H-4723
  • HR 376
  • HR-376
  • LM 2717
  • LM-2717

Pharmacology

Indication

Clobazam is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older.23

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofAnxiety••• •••••
Management ofCatamenial epilepsy••• •••••
Adjunct therapy in management ofRefractory status epilepticus••• •••••
Adjunct therapy in management ofSeizures••••••••••••••• •••••••••• •••••••••• •••• •••••••••••••• •••••••••••••
Adjunct therapy in management ofSeizures••••••••••••••••••••••• ••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Clobazam belongs to the benzodiazepine class of drugs.23 Clobazam acts on the GABAA receptor to increase GABAnergic transmission, particularly chloride conductance in neurons.9 This causes neuronal hyperpolarization, resulting in an increase in the action potential threshold and reducing neuron firing frequency.11,12 Consequently, the general neuronal activity of the central nervous system is depressed; therefore, clobazam can be used to treat diseases caused by excessive excitatory action potentials.12

The effect of clobazam 20 mg and 80 mg administered twice daily on QTc interval was evaluated in a randomized, evaluator-blinded, placebo-, and active-controlled (moxifloxacin 400 mg) parallel thorough QT study in 280 healthy subjects. In a study with demonstrated ability to detect small effects, the upper bound of the one-sided 95% confidence interval for the largest placebo-adjusted, baseline-corrected QTc based on the Fridericia correction method was below 10 ms, the threshold for regulatory concern. Thus, at a dose two times the maximum recommended dose, clobazam did not prolong the QTc interval to any clinically relevant extent.23

Mechanism of action

The exact mechanism of action for clobazam, a 1,5-benzodiazepine, is not fully understood but is thought to involve the potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABAA receptor.23 Specifically, clobazam binds to the interface of the α2 and γ2-subunit of the GABAA receptor.9 It has a great affinity for the α2 subunit than the α1 subunit compared to other 1,4‐benzodiazepines.10Binding of clobazam to the GABAA receptor causes chloride channels to open, resulting in an influx of chloride and thus hyperpolarization of neurons.9

TargetActionsOrganism
AGABA(A) Receptor
positive allosteric modulator
Humans
AGABA(A) Receptor Benzodiazepine Binding Site
ligand
Humans
Absorption

The peak plasma levels (Cmax) and the area under the curve (AUC) of clobazam are dose-proportional over the dose range of 10-80 mg following single- or multiple-dose administration of ONFI. Based on a population pharmacokinetic analysis, the pharmacokinetics of clobazam are linear from 5-160 mg/day.23

Clobazam is rapidly and extensively absorbed following oral administration. The time to peak concentrations (Tmax) of clobazam tablets under fasted conditions ranged from 0.5 to 4 hours after single- or multiple-dose administrations. The relative bioavailability of clobazam tablets compared to an oral solution is approximately 100%. After single-dose administration of the oral suspension under fasted conditions, the Tmax ranged from 0.5 to 2 hours. Based on exposure (Cmax and AUC) of clobazam, clobazam tablets and suspension were shown to have similar bioavailability under fasted conditions. The administration of clobazam tablets with food or when crushed in applesauce does not affect absorption. Although not studied, the oral bioavailability of the oral suspension is unlikely to be affected under fed conditions.23

Volume of distribution

Clobazam is lipophilic and distributes rapidly throughout the body. The apparent volume of distribution at steady state was approximately 100 L.23

Protein binding

The in vitro plasma protein binding of clobazam and N-desmethylclobazam is approximately 80-90% and 70%, respectively.23

Metabolism

Clobazam is extensively metabolized in the liver via N-demethylation and hydroxylation to form two major metabolites, N-desmethylclobazam (norclobazam) and 4'-hydroxyclobazam, respectively, with approximately 2% of the dose recovered in urine and 1% in feces as an unchanged drug.23,13 The N-demethylation reaction is catalyzed primarily by CYP3A4 and to a lesser extent by CYP2C19 and CYP2B6. N-desmethylclobazam, an active metabolite, is the major circulating metabolite in humans, and at therapeutic doses, plasma concentrations are 3-5 times higher than those of the parent compound. Based on animal and in vitro receptor binding data, estimates of the relative potency of N-desmethylclobazam compared to the parent compound range from 1/5 to equal potency. N-desmethylclobazam is extensively hydroxylated, mainly by CYP2C19. N-desmethylclobazam and its metabolites comprise ~94% of the total drug-related components in urine.23. The formation of 4'-hydroxyclobazam is facilitated by CYP2C18 and CYP2C19.13

The polymorphic CYP2C19 is the major contributor to the metabolism of the pharmacologically active N-desmethylclobazam. In CYP2C19 poor metabolizers, levels of N-desmethylclobazam were 5-fold higher in plasma and 2- to 3-fold higher in the urine than in CYP2C19 extensive metabolizers.23

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Route of elimination

N-desmethylclobazam and its metabolites comprise ~94% of the total drug-related components in urine. Following a single oral dose of radiolabeled drug, approximately 11% of the dose was excreted in the feces and approximately 82% was excreted in the urine.23

Half-life

The estimated mean elimination half-lives (t½) of clobazam and N-desmethylclobazam were 36-42 hours and 71-82 hours, respectively.23

Clearance

After a 20 to 40 mg/day administration of clobazam, the oral clearance is calculated to be 1.9 to 2.3 L/h.8

Adverse Effects
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Toxicity

Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see Warnings and Precautions (5.8) and Clinical Considerations]. Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association between benzodiazepines and major birth defects.23

Administration of clobazam to pregnant rats and rabbits during the period of organogenesis or to rats throughout pregnancy and lactation resulted in developmental toxicity, including increased incidences of fetal malformations and mortality, at plasma exposures for clobazam and its major active metabolite, N-desmethylclobazam, below those expected at therapeutic doses in patients. Data for other benzodiazepines suggest the possibility of long-term effects on neurobehavioral and immunological function in animals following prenatal exposure to benzodiazepines at clinically relevant doses. ONFI should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Advise a pregnant woman and women of childbearing age of the potential risk to a fetus.23

Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. Monitor neonates exposed to clobazam during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to clobazam during pregnancy for signs of withdrawal. Manage these neonates accordingly [see Warnings and Precautions (5.8)].23

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.23

Administration of clobazam to rats prior to and during mating and early gestation resulted in adverse effects on fertility and early embryonic development at plasma exposures for clobazam and its major active metabolite, N-desmethylclobazam, below those in humans at the MRHD [see Nonclinical Toxicology (13.1)].23

In a study in which clobazam (0, 4, 36, or 120 mg/kg/day) was orally administered to rats during the juvenile period of development (postnatal days 14 to 48), adverse effects on growth (decreased bone density and bone length) and behavior (altered motor activity and auditory startle response; learning deficit) were observed at the high dose. The effect on bone density, but not on behavior, was reversible when the drug was discontinued. The no-effect level for juvenile toxicity (36 mg/kg/day) was associated with plasma exposures (AUC) to clobazam and its major active metabolite, N-desmethylclobazam, less than those expected at therapeutic doses in pediatric patients.23

In mice, oral administration of clobazam (0, 6, 12, or 24 mg/kg/day) for 2 years did not result in an increase in tumors. The highest dose tested was approximately 3 times the maximum recommended human dose (MRHD) of 40 mg/day, based on body surface area (mg/m2).23

In rats, oral administration of clobazam for 2 years resulted in increases in tumors of the thyroid gland (follicular cell adenoma and carcinoma) and liver (hepatocellular adenoma) at the mid and high doses. The low dose, not associated with an increase in tumors, was associated with plasma exposures (AUC) for clobazam and its major active metabolite, N-desmethylclobazam, less than that in humans at the MRHD.23

Clobazam and the major active metabolite, N-desmethylclobazam, were negative for genotoxicity, based on data from a battery of in vitro (bacteria reverse mutation, mammalian clastogenicity) and in vivo (mouse micronucleus) assays.23

In a fertility study in which clobazam (50, 350, or 750 mg/kg/day, corresponding to 12, 84, and 181 times the oral Maximum Recommended Human Dose, MRHD, of 40 mg/day based on mg/m2 body surface) was orally administered to male and female rats prior to and during mating and continuing in females to gestation day 6, increases in abnormal sperm and pre-implantation loss were observed at the highest dose tested. The no-effect level for fertility and early embryonic development in rats was associated with plasma exposures (AUC) for clobazam and its major active metabolite, N-desmethylclobazam, less than those in humans at the maximum recommended human dose of 40 mg/day.23

Clobazam is a benzodiazepine and a CNS depressant with a potential for abuse and addiction. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. Abuse and misuse of benzodiazepines may lead to addiction.23

Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. Benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders [see Warnings and Precautions (5.2)].23

The following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo.23

The following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. Death is more often associated with polysubstance use (especially benzodiazepines with other CNS depressants such as opioids and alcohol).23

The World Health Organization epidemiology database contains reports of drug abuse, misuse, and overdoses associated with clobazam.23

Clobazam may produce physical dependence from continued therapy. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening.23

Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use [see Warnings and Precautions (5.3)]. In clinical trials, cases of dependency were reported following the abrupt discontinuation of clobazam.23

Acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g.,nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis,hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. More severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality.23

Protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. Protracted withdrawal symptoms may last weeks to more than 12 months. As a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used.23

Tolerance to clobazam may develop from continued therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Tolerance to the therapeutic effect of clobazam may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.23

Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal [see Warnings and Precautions (5.2)]. Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raises the concern that additional drugs and/or alcohol are involved in the overdosage.23

In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway maintenance. Flumazenil, a specific benzodiazepine receptor antagonist indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic antidepressants) and in patients with long-term benzodiazepine use and physical dependency. The risk of withdrawal seizures with flumazenil may be increased in patients with epilepsy. Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus). If the decision is made to use flumazenil, it should be used as an adjunct to, not as a substitute for, supportive management of benzodiazepine overdosage. See the flumazenil injection Prescribing Information.23

Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.23

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2C19CYP2C19*2(A;A) / (A;G)G > A/CADR Directly StudiedPatients with this genotype have reduced metabolism of clobazam.Details
Cytochrome P450 2C19CYP2C19*2ANot Available681G>AADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*2BNot Available681G>AADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*3Not Available636G>AADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*4Not Available1A>GADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*5Not Available1297C>TADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*6Not Available395G>AADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*7Not Available19294T>AADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*22Not Available557G>C / 991A>GADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*24Not Available99C>T / 991A>G  … show all ADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*35Not Available12662A>GADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of sedation, somnolence, and CNS depression can be increased when Clobazam is combined with 1,2-Benzodiazepine.
AbacavirClobazam may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Clobazam can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Clobazam can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Clobazam.
Food Interactions
  • Avoid alcohol. Alcohol increases clobazam absorption by 50%.
  • Take with or without food. The absorption is unaffected by food.

Products

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Product Images
International/Other Brands
Aedon (Sanofi-Aventis) / Castilium (Sanofi-Aventis) / Clobam (Square) / Clobamax (Sherfarma) / Frisium (Sanofi-Aventis) / Grifoclobam (Chile) / Mystan (Dainippon Sumitomo) / Noiafren (Sanofi Aventis) / Sederlona / Urbanil (Sanofi-Aventis) / Urbanol (Sanofi-Aventis) / Urbanyl (Sanofi-Aventis) / Venium (Hudson)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Clobazam-10Tablet10 mgOralPro Doc Limitee2003-12-092017-05-05Canada flag
Frisium Tab 10mgTablet10 mg / tabOralHoechst Canada Inc.1991-12-311996-08-29Canada flag
Frisium Tablet 10mgTablet10 mgOralLundbeck Pharmaceuticals Llc1997-03-242018-08-31Canada flag
Frisium Tablets 10mgTablet10 mgOralHoechst Roussel Canada Inc.1994-12-311999-08-11Canada flag
OnfiTablet10 mg/1OralLundbeck Pharmaceuticals Llc2013-12-10Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-clobazamTablet10 mgOralApotex Corporation2001-11-28Not applicableCanada flag
ClobazamTablet20 mg/1OralNovadoz Pharmaceuticals Llc2022-06-10Not applicableUS flag
ClobazamTablet20 mg/1OralUpsher-Smith Laboratories, LLC2018-10-22Not applicableUS flag
ClobazamTablet10 mg/1OralAscend Laboratories, LLC2019-09-07Not applicableUS flag
ClobazamSuspension2.5 mg/1mLOralAmneal Pharmaceuticals NY LLC2018-10-22Not applicableUS flag

Categories

ATC Codes
N05BA09 — Clobazam
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
Not Available
Direct Parent
Benzodiazepines
Alternative Parents
1,4-diazepines / Benzene and substituted derivatives / Aryl chlorides / 1,3-dicarbonyl compounds / Tertiary carboxylic acid amides / Lactams / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organochlorides
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Substituents
1,3-dicarbonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Benzodiazepine / Carbonyl group / Carboxamide group / Carboxylic acid derivative
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organochlorine compound, 1,4-benzodiazepinone (CHEBI:31413)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
2MRO291B4U
CAS number
22316-47-8
InChI Key
CXOXHMZGEKVPMT-UHFFFAOYSA-N
InChI
InChI=1S/C16H13ClN2O2/c1-18-13-8-7-11(17)9-14(13)19(16(21)10-15(18)20)12-5-3-2-4-6-12/h2-9H,10H2,1H3
IUPAC Name
7-chloro-1-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-2,4-dione
SMILES
CN1C2=C(C=C(Cl)C=C2)N(C2=CC=CC=C2)C(=O)CC1=O

References

Synthesis Reference

Hauptmann, K.H., Weber, K.-H., Zeile, K., Danneberg, P. and Giesemann, R.; South African Patent 68/0803; February 7,1968; assigned to Boehringer lngelheim GmbH, Germany.

General References
  1. Freche C: [Study of an anxiolytic, clobazam, in otorhinolaryngology in psychosomatic pharyngeal manifestations]. Sem Hop Ther. 1975 Apr;51(4):261-3. [Article]
  2. Authors unspecified: Clobazam in treatment of refractory epilepsy: the Canadian experience. A retrospective study. Canadian Clobazam Cooperative Group. Epilepsia. 1991 May-Jun;32(3):407-16. [Article]
  3. Wildin JD, Pleuvry BJ, Mawer GE, Onon T, Millington L: Respiratory and sedative effects of clobazam and clonazepam in volunteers. Br J Clin Pharmacol. 1990 Feb;29(2):169-77. [Article]
  4. Kilpatrick C, Bury R, Fullinfaw R, Moulds R: Clobazam in the treatment of epilepsy. Clin Exp Neurol. 1987;23:139-44. [Article]
  5. Giarratano M, Standley K, Benbadis SR: Clobazam for treatment of epilepsy. Expert Opin Pharmacother. 2012 Feb;13(2):227-33. doi: 10.1517/14656566.2012.647686. Epub 2012 Jan 13. [Article]
  6. Yang LP, Scott LJ: Clobazam : in patients with Lennox-Gastaut syndrome. CNS Drugs. 2012 Nov;26(11):983-91. doi: 10.1007/s40263-012-0007-0. [Article]
  7. Walzer M, Bekersky I, Blum RA, Tolbert D: Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Pharmacotherapy. 2012 Apr;32(4):340-53. doi: 10.1002/j.1875-9114.2012.01028.x. Epub 2012 Mar 15. [Article]
  8. Tolbert D, Larsen F: A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam. J Clin Pharmacol. 2019 Jan;59(1):7-19. doi: 10.1002/jcph.1313. Epub 2018 Oct 4. [Article]
  9. Gauthier AC, Mattson RH: Clobazam: A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy. CNS Neurosci Ther. 2015 Jul;21(7):543-8. doi: 10.1111/cns.12399. Epub 2015 Apr 28. [Article]
  10. Jensen HS, Nichol K, Lee D, Ebert B: Clobazam and its active metabolite N-desmethylclobazam display significantly greater affinities for alpha(2)- versus alpha(1)-GABA(A)-receptor complexes. PLoS One. 2014 Feb 12;9(2):e88456. doi: 10.1371/journal.pone.0088456. eCollection 2014. [Article]
  11. Nakamura F, Suzuki S, Nishimura S, Yagi K, Seino M: Effects of clobazam and its active metabolite on GABA-activated currents in rat cerebral neurons in culture. Epilepsia. 1996 Aug;37(8):728-35. doi: 10.1111/j.1528-1157.1996.tb00643.x. [Article]
  12. Stafstrom CE, Carmant L: Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harb Perspect Med. 2015 Jun 1;5(6):a022426. doi: 10.1101/cshperspect.a022426. [Article]
  13. Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
  14. Guerreiro CA: Clobazam: the phoenix drug (from the very old to the brand new). Indian J Med Res. 2014 Aug;140(2):163-4. [Article]
  15. Sankar R: GABA(A) receptor physiology and its relationship to the mechanism of action of the 1,5-benzodiazepine clobazam. CNS Drugs. 2012 Mar 1;26(3):229-44. doi: 10.2165/11599020-000000000-00000. [Article]
  16. Pernea M, Sutcliffe AG: Clobazam and Its Use in Epilepsy. Pediatr Rep. 2016 Jun 15;8(2):6516. doi: 10.4081/pr.2016.6516. eCollection 2016 Jun 15. [Article]
  17. Faulkner MA: Comprehensive overview: efficacy, tolerability, and cost-effectiveness of clobazam in Lennox-Gastaut syndrome. Ther Clin Risk Manag. 2015 Jun 8;11:905-14. doi: 10.2147/TCRM.S55930. eCollection 2015. [Article]
  18. Humayun MJ, Samanta D, Carson RP: Clobazam. . [Article]
  19. Tanabe T, Awaya Y, Matsuishi T, Iyoda K, Nagai T, Kurihara M, Yamamoto K, Minagawa K, Maekawa K: Management of and prophylaxis against status epilepticus in children with severe myoclonic epilepsy in infancy (SMEI; Dravet syndrome)--a nationwide questionnaire survey in Japan. Brain Dev. 2008 Nov;30(10):629-35. doi: 10.1016/j.braindev.2008.03.002. [Article]
  20. Sivakumar S, Ibrahim M, Parker D Jr, Norris G, Shah A, Mohamed W: Clobazam: An effective add-on therapy in refractory status epilepticus. Epilepsia. 2015 Jun;56(6):e83-9. doi: 10.1111/epi.13013. Epub 2015 May 12. [Article]
  21. Feely M, Calvert R, Gibson J: Clobazam in catamenial epilepsy. A model for evaluating anticonvulsants. Lancet. 1982 Jul 10;2(8289):71-3. doi: 10.1016/s0140-6736(82)91691-9. [Article]
  22. Rickels K, Brown AS, Cohen D, Harris H, Hurowitz A, Lindenbaum EJ, Ross HA, Weinstock R, Wiseman K, Zal M: Clobazam and diazepam in anxiety. Clin Pharmacol Ther. 1981 Jul;30(1):95-100. doi: 10.1038/clpt.1981.132. [Article]
  23. FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
  24. DailyMed Label: ONFI (clobazam) oral suspension or tablets, CIV [Link]
  25. Clobazam MSDS LGC [Link]
  26. Clobazam (T3D4564) [Link]
  27. Health Canada Approved Drug Proucts: APO-CLOBAZAM (Clobazam) tablets, for oral use [Link]
Human Metabolome Database
HMDB0014493
KEGG Drug
D01253
PubChem Compound
2789
PubChem Substance
46506115
ChemSpider
2687
BindingDB
50247888
RxNav
21241
ChEBI
31413
ChEMBL
CHEMBL70418
ZINC
ZINC000000001175
Therapeutic Targets Database
DAP000672
PharmGKB
PA10888
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Clobazam
FDA label
Download (595 KB)
MSDS
Download (57.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAnxiety / Epilepsy1
4RecruitingTreatmentDrug-resistant Epilepsy1
4Unknown StatusTreatmentEpilepsy2
4Unknown StatusTreatmentRefractory Epilepsy1
3CompletedBasic ScienceBack Pain Lower Back1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
SolutionOral2.5 mg/1mL
SuspensionOral2.5 mg/1mL
SuspensionOral1 mg/ml
SuspensionOral2 mg/ml
Capsule
TabletOral10.00 mg
TabletOral
TabletOral20 mg
TabletOral10 mg / tab
TabletOral10 mg
TabletOral1000000 mg
TabletOral2000000 mg
TabletOral10 mg/1
TabletOral20 mg/1
TabletOral5 mg/1
FilmOral10 mg/1
FilmOral20 mg/1
FilmOral5 mg/1
SuspensionOral0.25 g
Prices
Unit descriptionCostUnit
Apo-Clobazam 10 mg Tablet0.23USD tablet
Novo-Clobazam 10 mg Tablet0.23USD tablet
Pms-Clobazam 10 mg Tablet0.23USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8603514No2013-12-102024-04-03US flag
US8765167No2014-07-012024-02-20US flag
US11541002No2019-09-052039-09-05US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)182-185ºCL44888
water solubility188 mg/LL44983
logP2.12HENCZI,M ET AL. (1995),L44973
Predicted Properties
PropertyValueSource
Water Solubility0.164 mg/mLALOGPS
logP2.14ALOGPS
logP2.55Chemaxon
logS-3.3ALOGPS
pKa (Strongest Acidic)5.82Chemaxon
pKa (Strongest Basic)-6.7Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area40.62 Å2Chemaxon
Rotatable Bond Count1Chemaxon
Refractivity80.3 m3·mol-1Chemaxon
Polarizability30.07 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.99
Blood Brain Barrier+0.9904
Caco-2 permeable+0.7487
P-glycoprotein substrateNon-substrate0.5733
P-glycoprotein inhibitor INon-inhibitor0.5462
P-glycoprotein inhibitor IINon-inhibitor0.9204
Renal organic cation transporterNon-inhibitor0.7373
CYP450 2C9 substrateNon-substrate0.7058
CYP450 2D6 substrateNon-substrate0.8607
CYP450 3A4 substrateSubstrate0.6871
CYP450 1A2 substrateNon-inhibitor0.6829
CYP450 2C9 inhibitorNon-inhibitor0.5296
CYP450 2D6 inhibitorNon-inhibitor0.8908
CYP450 2C19 inhibitorNon-inhibitor0.5791
CYP450 3A4 inhibitorInhibitor0.7008
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5308
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.7846
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.7313 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9896
hERG inhibition (predictor II)Non-inhibitor0.8651
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (11.4 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-053r-0290000000-85c722aae16a6c4f1e1a
Mass Spectrum (Electron Ionization)MSsplash10-0pb9-6392000000-a76f30f353b3407df0c6
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0090000000-3b46d60abcc8dfacf4d8
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0019000000-71512d7a18cf60430dd9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0092000000-e687a1e3760fb870dbc9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0090000000-d450ded1f22039f00b63
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0ab9-0190000000-e4211cbc2957a587e3d3
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05fr-0590000000-51f4fa0445c2d047ef6b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0g4j-1960000000-a89e1c91bfa7b974be48
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014j-4920000000-93c0877b3acf519d2b98
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-016u-7900000000-bc29714be08b6ae4120b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0hi6-9600000000-7c6a3974d95a0015757e
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-0029000000-f3f89ed52781ec5f7ed4
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-0090000000-689f7c9d0270ead27fff
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-0049000000-588c79578f36559849c9
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-1090000000-3089d37d99ecd3cb770e
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0k92-2940000000-a19c4fc978ce4a63614d
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-1090000000-0e3db2659f3f3c3840db
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-168.6874803
predicted
DarkChem Lite v0.1.0
[M-H]-164.7596
predicted
DeepCCS 1.0 (2019)
[M+H]+169.4000803
predicted
DarkChem Lite v0.1.0
[M+H]+167.11758
predicted
DeepCCS 1.0 (2019)
[M+Na]+169.0764803
predicted
DarkChem Lite v0.1.0
[M+Na]+173.21074
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
Curator comments
The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [Article]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
Curator comments
Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
  2. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
  2. Tolbert D, Larsen F: A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam. J Clin Pharmacol. 2019 Jan;59(1):7-19. doi: 10.1002/jcph.1313. Epub 2018 Oct 4. [Article]
  3. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Huddart R, Leeder JS, Altman RB, Klein TE: PharmGKB summary: clobazam pathway, pharmacokinetics. Pharmacogenet Genomics. 2018 Apr;28(4):110-115. doi: 10.1097/FPC.0000000000000327. [Article]
  2. Walzer M, Bekersky I, Blum RA, Tolbert D: Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Pharmacotherapy. 2012 Apr;32(4):340-53. doi: 10.1002/j.1875-9114.2012.01028.x. Epub 2012 Mar 15. [Article]
  3. Tolbert D, Bekersky I, Chu HM, Ette EI: Drug-metabolism mechanism: Knowledge-based population pharmacokinetic approach for characterizing clobazam drug-drug interactions. J Clin Pharmacol. 2016 Mar;56(3):365-74. doi: 10.1002/jcph.603. Epub 2015 Sep 29. [Article]
  4. Flockhart Table of Drug Interactions [Link]
  5. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
Molecular Weight
55710.075 Da
References
  1. Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. de Leon J, Spina E, Diaz FJ: Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies. Ther Drug Monit. 2013 Feb;35(1):30-47. doi: 10.1097/FTD.0b013e31827ada88. [Article]
  2. Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
  3. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
  2. de Leon J, Spina E, Diaz FJ: Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies. Ther Drug Monit. 2013 Feb;35(1):30-47. doi: 10.1097/FTD.0b013e31827ada88. [Article]
  3. Huddart R, Leeder JS, Altman RB, Klein TE: PharmGKB summary: clobazam pathway, pharmacokinetics. Pharmacogenet Genomics. 2018 Apr;28(4):110-115. doi: 10.1097/FPC.0000000000000327. [Article]
  4. Clobazam FDA label [Link]
  5. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Upregulator
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A4
Uniprot ID
P22310
Uniprot Name
UDP-glucuronosyltransferase 1-4
Molecular Weight
60024.535 Da
References
  1. FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 3 lacks trans...
Gene Name
UGT1A6
Uniprot ID
P19224
Uniprot Name
UDP-glucuronosyltransferase 1-6
Molecular Weight
60750.215 Da
References
  1. FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as...
Gene Name
UGT2B4
Uniprot ID
P06133
Uniprot Name
UDP-glucuronosyltransferase 2B4
Molecular Weight
60512.035 Da
References
  1. FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Patsalos PN, Zugman M, Lake C, James A, Ratnaraj N, Sander JW: Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non-protein-bound concentrations. Epilepsia. 2017 Jul;58(7):1234-1243. doi: 10.1111/epi.13802. Epub 2017 May 24. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Patsalos PN, Zugman M, Lake C, James A, Ratnaraj N, Sander JW: Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non-protein-bound concentrations. Epilepsia. 2017 Jul;58(7):1234-1243. doi: 10.1111/epi.13802. Epub 2017 May 24. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]

Drug created at June 13, 2005 13:24 / Updated at May 27, 2024 02:37