Midazolam

Identification

Summary

Midazolam is a short-acting benzodiazepine with rapid onset that is commonly used in seizures, anesthesia and anxiety disorders.

Brand Names
Buccolam, Busulfex, Nayzilam, Seizalam
Generic Name
Midazolam
DrugBank Accession Number
DB00683
Background

Midazolam is a short-acting hypnotic-sedative drug with anxiolytic, muscle relaxant, anticonvulsant, sedative, hypnotic, and amnesic properties.6 It belongs to a class of drugs called benzodiazepines. This drug is unique from others in this class due to its rapid onset of effects and short duration of action.6 Midazolam is available by oral, rectal, intranasal, intramuscular (IM), and intravenous (IV) routes and has been used in various biomedical applications, including dentistry, cardiac surgery, and endoscopic procedures as pre-anesthetic medication, and as an adjunct to local anesthesia.21

This drug was initially approved by the US FDA in 1985, and has been approved for various indications since.19 In late 2018, the intramuscular preparation was approved by the FDA for the treatment of status epilepticus in adults.19 In May 2019, the nasal spray of midazolam was approved for the acute treatment of distinctive intermittent, stereotypic seizure episodes in patients 12 years of age and older.8 Midazolam is considered a schedule IV drug in the United States due to the low potential for abuse and low risk of dependence.10

Type
Small Molecule
Groups
Approved, Illicit
Structure
Weight
Average: 325.767
Monoisotopic: 325.078203343
Chemical Formula
C18H13ClFN3
Synonyms
  • Midazolam
  • Midazolamum
External IDs
  • Dea No. 2884
  • Ro 21-3981/001
  • Ro 21-3981/003

Pharmacology

Indication

Midazolam has different indications depending on its formulation by the FDA.

Nasal

For the nasal spray formulation, midazolam is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 12 years of age and older.13

Intravenous

For the intravenous injection formulation, midazolam is indicated as an agent for sedation/anxiolysis/amnesia and prior to or during diagnostic, therapeutic or endoscopic procedures, such as bronchoscopy, gastroscopy, cystoscopy, coronary angiography, cardiac catheterization, oncology procedures, radiologic procedures, suture of lacerations and other procedures either alone or in combination with other CNS depressants.14 The sedative, anxiolytic and amnestic use of midazolam can also be employed pre-operatively.14 It can also be indicated for induction of general anesthesia, before administration of other anesthetic agents or as a component of intravenous supplementation of nitrous oxide and oxygen for a balanced anesthesia.14 A relatively narrower dose range of midazolam and a shorter period of induction can be achieved if midazolam is combined with narcotic premedication.14 Finally, midazolam can be indicated as a continous intravenous infusion for sedation of intubated and mechanically ventilated patients as a component of anesthesia or during treatment in a critical care setting.14

Intramuscular

For the intramusuclar injection formulation, midazolam is indicated for preoperative sedation/anxiolysis/amnesia or for treatment of status epilepticus in adults.14,15

Oral

Midazolam syrup is indicated for use in pediatric patients for sedation, anxiolysis and amnesia prior to diagnostic, therapeutic or endoscopic procedures or before induction of anesthesia. It is only approved in monitored settings only and not for chronic or home use.11

In Europe, a buccal formulation of midazolam is also approved for the treatment of prolonged, acute, convulsive seizures in infants, toddlers, children and adolescents (from 3 months to < 18 years). For infants between 3-6 months of age treatment should be in a hospital setting where monitoring is possible and resuscitation equipment is available.16

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofEpileptic seizure••••••••••••••••••••••• •••••••••••• ••••••• ••••••••••••
Treatment ofStatus epilepticus••••••••••••••••••••••••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

General effects

Midazolam is a short-acting benzodiazepine central nervous system (CNS) depressant. Pharmacodynamic properties of midazolam and its metabolites, which are similar to those of other benzodiazepine drugs, include sedative, anxiolytic, amnestic, muscle relaxant, as well as hypnotic activities.20 Benzodiazepines enhance the inhibitory action of the amino acid neurotransmitter gamma-aminobutyric acid (GABA). Receptors for GABA are targeted by many important drugs that affect GABA function and are commonly used in the treatment of anxiety disorder, epilepsy, insomnia, spasticity, and aggressive behavior.7

Sedation and memory

The onset of sedation after intramuscular administration in adults is 15 minutes, with maximal sedation occurring 30-60 minutes after injection.Label In one study of adults, when tested the following day, 73% of the patients who were administered midazolam intramuscularly had no recollection of memory cards shown 30 minutes following drug administration; 40% had no recollection of the memory cards shown 60 minutes after drug administration. Onset time of sedative effects in pediatric patients begins within 5 minutes and peaks at 15-30 minutes depending upon the dose administered. In the pediatric population, up to 85% had no memory of pictures shown after receiving intramuscular midazolam compared to 5% of the placebo control group.20

Sedation in both adult and pediatric patients is reached within 3 to 5 minutes post intravenous (IV) injection. The time of onset is affected by the dose administered and the simultaneous administration of narcotic pre-medication. Seventy-one (71%) percent of the adult patients in clinical endoscopy studies had no memory of insertion of the endoscope; 82% of the patients had no memory of withdrawal of the endoscope.14

Anesthesia induction

When midazolam is administered intravenously (IV) for anesthetic induction, induction of anesthesia occurs in about 1.5 minutes when narcotic pre-medication has been given and in 2 to 2.5 minutes without narcotic pre-medication/ other sedative pre-medication. Impairment in a memory test was observed in 90% of the patients.14

Mechanism of action

The actions of benzodiazepines such as midazolam are mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which is one of the major inhibitory neurotransmitters in the central nervous system. Benzodiazepines increase the activity of GABA, thereby producing a sedating effect, relaxing skeletal muscles, and inducing sleep, anesthesia, and amnesia. Benzodiazepines bind to the benzodiazepine site on GABA-A receptors, which potentiates the effects of GABA by increasing the frequency of chloride channel opening.20 These receptors have been identified in different body tissues including the heart and skeletal muscle, although mainly appear to be present in the central nervous system.6

TargetActionsOrganism
AGABA(A) Receptor
positive allosteric modulator
Humans
AGABA(A) Receptor Benzodiazepine Binding Site
ligand
Humans
UAdenosine receptor A2a
potentiator
Humans
Absorption

Intramuscular

Following IM administration of a single 10 mg midazolam dose to healthy subjects, midazolam was absorbed with median Tmax (range) of 0.5 (0.25 to 0.5) hours; midazolam's mean (±SD) Cmax and AUC0-∞ were 113.9 (±30.9) ng/mL and 402.7 (±97.0) ng∙h/mL, respectively.15

Rectal

After rectal administration midazolam is absorbed rapidly. Maximum plasma concentration is reached within 30 minutes. The absolute bioavailability is approximately 50%.21

Intranasal Administration

Following the nasal administration of a single 5 mg midazolam dose to healthy adults, midazolam was absorbed with a median Tmax (range) of 17.3 (7.8 to 28.2) minutes; midazolam's mean (±SD) Cmax and AUC0-∞ were 54.7 (±30.4) ng/mL and 126.2 (±59) ng∙h/mL, respectively. The mean absolute bioavailability is approximately 44%.13

Oral

In pediatric patients from 6 months to <16 years old, the mean Tmax values across dose groups (0.25, 0.5, and 1.0 mg/kg) range from 0.17 to 2.65 hours. Midazolam also exhibits linear pharmacokinetics within this dose range (up to a maximum dose of 40 mg). Linearity was also demonstrated across the doses within the age group of 2 years to <12 years having 18 patients at each of the three doses. Due to first-pass metabolism, only 40-50% of the administered oral dose reaches the circulation.6 The absolute bioavailability of midazolam is about 36%, which is not affected by pediatric age or weight. Cmax and AUC0-∞ were also calculated to range from 28 to 201 ng/mL and 67.6 to 821 ng∙h/mL respectively.11

Buccal

After oromucosal administration midazolam is absorbed rapidly. Maximum plasma concentration is reached within 30 minutes in children. The absolute bioavailability of oromucosal midazolam is about 75% in adults. The bioavailability of oromucosal midazolam has been estimated at 87% in children with severe malaria and convulsions. Cmax and AUC0-∞ were also calculated to range from 87 to 148 ng/mL and 168 to 254 ng∙h/mL respectively.16

Volume of distribution

Female gender, old age, and obesity may increase the volume of distribution. Midazolam may also cross the placenta and has been detected in human milk and cerebrospinal fluid.Label,20

Intravenous administration

In pediatric patients (6 months to <16 years) receiving 0.15 mg/kg IV midazolam, the mean steady-state volume of distribution ranged from 1.24 to 2.02 L/kg.11 For healthy adult patients, the volume of distribution determined from six single-dose pharmacokinetic studies ranged from 1.0 to 3.1 L/kg.14

Intramuscular administration

The mean (±SD) apparent volume of distribution (Vz/F) of midazolam following a single IM dose of 10 mg midazolam was 2117 (±845.1) mL/kg in healthy subjects.15

Intranasal

The estimated total volume of distribution of midazolam is 226.5 L.13

Buccal

The steady-state volume of distribution following oromucosal administration is estimated to be 5.3 l/kg.16

Protein binding

In adults and pediatric patients, midazolam is approximately 97% bound to plasma protein, principally albumin. In healthy volunteers, 1-hydroxy midazolam is bound to the extent of 89%.13

Metabolism

In vitro studies with human liver microsomes indicate that the biotransformation of midazolam is mediated by the cytochrome P450-3A4 (CYP3A4). This enzyme is present in gastrointestinal tract mucosa, as well as in the liver. The 1-hydroxy-midazolam (also termed alpha-hydroxymidazolam) metabolite comprises 60% to 70% of the biotransformation products of midazolam, while 4-hydroxy-midazolam constitutes 5% or less. Small amounts of a dihydroxy derivative have also been detected, but not quantified.15 Midazolam also undergoes N-glucuronidation via UGT1A4 after the process of hepatic oxidation by cytochrome enzymes.6

Studies of the intravenous administration of 1-hydroxy-midazolam in humans suggest that 1-hydroxymidazolam is at least as potent as the parent compound, and may contribute to the net pharmacologic activity of midazolam. In vitro studies have demonstrated that the affinities of 1- and 4-hydroxy-midazolam for the benzodiazepine receptor are approximately 20% and 7%, respectively, relative to midazolam.15

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Route of elimination

The α-hydroxymidazolam glucuronide conjugate of midazolam is excreted in the urine. No significant amount of parent drug or metabolites is found in urine before beta-glucuronidase and sulfatase deconjugation, suggesting that the urinary metabolites are excreted mainly as conjugates. The amount of midazolam excreted unchanged in the urine when given intravenously is less than 0.5%. 45% to 57% of the dose was excreted in the urine as 1-hydroxymethyl midazolam conjugate.15 The principal urinary excretion products are glucuronide conjugates of hydroxylated derivatives.15

Plasma clearance of midazolam is higher in patients that remain in the supine position, because of a 40-60 percent increase in hepatic blood flow during supination. Pregnancy may also increase the metabolism of midazolam.6

Half-life

Intravenous: Six single-dose pharmacokinetic studies involving healthy adults yield an elimination half-life of 1.8 to 6.4 hours (mean of approximately 3 hours).14

Intramuscular Following IM administration of 10 mg midazolam, the mean (±SD) elimination half-life of midazolam was 4.2 (±1.87) hours.15

Intranasal Following the administration of NAYZILAM in clinical trials, median midazolam and 1-hydroxy-midazolam elimination half-lives ranged from 2.1 to 6.2 hours and 2.7 to 7.2 hours, respectively, independent of dose.13

Oral The mean elimination half-life of midazolam ranged from 2.2 to 6.8 hours following single oral doses of 0.25, 0.5, and 1.0 mg/kg of midazolam HCl syrup.11

*Buccal The initial and terminal elimination half-lives are 27 and 204 minutes, respectively.16

Clearance

Intramuscular

Following IM administration of 10 mg midazolam, the apparent total body clearance (CL/F) of midazolam was 367.3 (±73.5) mL/hr/kg.15

Intravenous:

Six single-dose pharmacokinetic studies involving healthy adults yield a total clearance (Cl) of 0.25 to 0.54 L/hr/kg.14

Intranasal

Midazolam clearance was calculated to be 1.9 mL/min/kg

Oral Following a group of patients receiving the 0.15 mg/kg IV dose, the mean total clearance ranged from 9.3 to 11.0 mL/min/kg.11

*Buccal Plasma clearance of midazolam in children following oromucosal administration is 30 ml/kg/min.16

Adverse Effects
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Toxicity

LD50=215 mg/kg, in rats.MSDS

Overdose

Signs of overdose include sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma, and deleterious effects on vital signs. Serious cardiorespiratory adverse reactions have occurred, sometimes ending in death or permanent neurologic effects, after the administration of midazolam.Label

A note on cardiac and respiratory depression

After administration of midazolam, continuous monitoring of respiratory and cardiac function is recommended until the patient is in stable condition. Serious and life-threatening cardiorespiratory adverse reactions, including hypoventilation, airway obstruction, apnea, and hypotension have been reported with the use of midazolam. Patients should be monitored in a setting with immediate access to resuscitative drugs if they are required. Resuscitation equipment and personnel trained in their use and skilled in airway management should be available when midazolam is administered.Label

The usual recommended intramuscular pre-medicating doses of midazolam do not depress the ventilatory response to carbon dioxide stimulation to a clinically significant extent in adults. Intravenous induction doses of midazolam depress the ventilatory response to carbon dioxide stimulation for at least 15 minutes longer than the duration of ventilatory depression following administration of thiopental in adults. Impairment of ventilatory response to carbon dioxide is more severe in adult patients diagnosed with chronic obstructive pulmonary disease (COPD).20

A note on dependence

When midazolam is used in long-term sedation in the ICU (intensive care unit) or other settings, physical dependence on midazolam may develop. The risk of dependence increases with dose and duration of treatment; this risk is also greater in patients with a medical history of substance abuse.10

Special caution should be exercised when administering midazolam in the following populations

High-risk patients include adults over 60 years of age, chronically ill or debilitated patients, which may include patients with chronic respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired cardiac function, pediatric patients (especially those with cardiovascular instability). These high-risk patients require lower dosages and should be monitored on a continuous basis for early signs of alterations of vital functions, so that appropriate management may be administered.10

Mutagenesis

Midazolam was negative for genotoxicity during in vitro and in vivo assays.Label

Impairment of Fertility

When midazolam (0, 1, 4, or 16 mg/kg) was given orally to male and female rats before and during mating and continuing in females throughout gestation and lactation, no adverse effects on male or female fertility were observed. Midazolam plasma exposures (AUC) at the highest dose tested were approximately 6 times that in humans at the recomended human dose.Label

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

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 and CNS depression can be increased when Midazolam is combined with 1,2-Benzodiazepine.
AbacavirMidazolam may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Midazolam can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Midazolam can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Midazolam.
Food Interactions
  • Avoid alcohol. Midazolam may make your sleepiness or dizziness worse.
  • Avoid grapefruit products. Bioavailability of midazolam can increase.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Midazolam hydrochlorideW7TTW573JJ59467-96-8PLYSCVSCYOQVRP-UHFFFAOYSA-N
Midazolam maleate77520S18SE59467-94-6XYGVIBXOJOOCFR-BTJKTKAUSA-N
International/Other Brands
Anquil (General Pharma) / Benzosed (Pharmaceutical) / Dalam (Richmond) / Damizol (Specifar) / Demizolam (Dem Ilaç) / Doricum (Roche) / Dormicum (Roche) / Dormid (Scott) / Dormipron (Chalver) / Dormire (Cristália) / Dormitol (Square) / Dormixal (Demo) / Dormonid (Roche) / Drimnorth (Northia) / Epistatus (IFET) / Flormidal (Galenika) / Fulsed (Ranbaxy) / Fulsed Injection (Terapia) / Garen (Bio-Pharma) / Gobbizolam (Gobbi) / Hipnazolam (EMS) / Hipnoz (Pharos) / Hypnofast (Incepta) / Hypnovel (Roche) / Ipnovel (Roche) / Nocturna (Lafi) / Setam (Rimsa) / Talentum (Fisiopharma) / Terap (Sanitas) / Versed (Roche)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BuccolamSolution5 mgBuccalNeuraxpharm Pharmaceuticals S.L.2022-05-04Not applicableEU flag
BuccolamSolution7.5 mgBuccalNeuraxpharm Pharmaceuticals S.L.2016-09-08Not applicableEU flag
BuccolamSolution10 mgBuccalNeuraxpharm Pharmaceuticals S.L.2022-05-04Not applicableEU flag
BuccolamSolution2.5 mgBuccalNeuraxpharm Pharmaceuticals S.L.2022-05-04Not applicableEU flag
BuccolamSolution5 mgBuccalNeuraxpharm Pharmaceuticals S.L.2016-09-08Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-midazolam Injectable 1 mg/mlLiquid1 mg / mLIntramuscular; IntravenousApotex Corporation2001-04-102013-08-02Canada flag
Apo-midazolam Injectable 5 mg/mlLiquid5 mg / mLIntramuscular; IntravenousApotex Corporation2001-04-102013-08-02Canada flag
MidazolamInjection5 mg/1mLIntramuscular; IntravenousSun Pharmaceutical Industries Limited2012-08-082018-06-29US flag
MidazolamInjection, solution1 mg/1mLIntramuscular; IntravenousFresenius Kabi USA, LLC2000-07-14Not applicableUS flag
MidazolamInjection5 mg/1mLIntramuscular; IntravenousGeneral Injectables and Vaccines, Inc.2017-11-282021-09-30US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Midazolam HClMidazolam hydrochloride (1 mg/1mL)Injection, solutionIntravenousCantrell Drug Company2013-06-28Not applicableUS flag
Midazolam HClMidazolam hydrochloride (0.5 mg/1mL)Injection, solutionIntravenousCantrell Drug Company2014-09-03Not applicableUS flag
MIDOLAM 15 MG/3 ML IM/IV REKTAL COZELTI ICEREN AMPUL, 5 ADETMidazolam (15 mg/3ml)InjectionIntramuscular; IntravenousPHARMADA İLAÇ SAN. VE TİC. A.Ş.2020-03-172024-01-23Turkey flag
MIDOLAM 5 MG/1 ML IM/IV REKTAL COZELTI ICEREN AMPUL, 5 ADETMidazolam (5 mg/1ml)InjectionIntramuscular; IntravenousPHARMADA İLAÇ SAN. VE TİC. A.Ş.2020-03-172024-01-23Turkey flag
MIDOLAM 50 MG/10 ML IM/IV REKTAL COZELTI ICEREN AMPUL, 5 ADETMidazolam (50 mg/10ml)InjectionIntramuscular; IntravenousPHARMADA İLAÇ SAN. VE TİC. A.Ş.2019-11-262024-01-23Turkey flag

Categories

ATC Codes
N05CD08 — Midazolam
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as imidazo[1,5-a][1,4]benzodiazepines. These are compounds containing an imidazole ring and a 1,4-benzodiazepine ring system, both sharing one nitrogen atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
1,4-benzodiazepines
Direct Parent
Imidazo[1,5-a][1,4]benzodiazepines
Alternative Parents
Fluorobenzenes / 1,4-diazepines / N-substituted imidazoles / Aryl fluorides / Aryl chlorides / Heteroaromatic compounds / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
Aromatic heteropolycyclic compound / Aryl chloride / Aryl fluoride / Aryl halide / Azacycle / Azole / Benzenoid / Fluorobenzene / Halobenzene / Heteroaromatic compound
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
diazepine (CHEBI:6931)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
R60L0SM5BC
CAS number
59467-70-8
InChI Key
DDLIGBOFAVUZHB-UHFFFAOYSA-N
InChI
InChI=1S/C18H13ClFN3/c1-11-21-9-13-10-22-18(14-4-2-3-5-16(14)20)15-8-12(19)6-7-17(15)23(11)13/h2-9H,10H2,1H3
IUPAC Name
12-chloro-9-(2-fluorophenyl)-3-methyl-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaene
SMILES
CC1=NC=C2CN=C(C3=CC=CC=C3F)C3=C(C=CC(Cl)=C3)N12

References

Synthesis Reference
US6262260
General References
  1. Skerritt JH, Johnston GA: Enhancement of GABA binding by benzodiazepines and related anxiolytics. Eur J Pharmacol. 1983 May 6;89(3-4):193-8. [Article]
  2. Isojarvi JI, Tokola RA: Benzodiazepines in the treatment of epilepsy in people with intellectual disability. J Intellect Disabil Res. 1998 Dec;42 Suppl 1:80-92. [Article]
  3. Garratt JC, Gent JP, Feely M, Haigh JR: Can benzodiazepines be classified by characterising their anticonvulsant tolerance-inducing potential? Eur J Pharmacol. 1988 Jan 5;145(1):75-80. [Article]
  4. Tokunaga S, Takeda Y, Shinomiya K, Hirase M, Kamei C: Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. J Pharmacol Sci. 2007 Feb;103(2):201-6. Epub 2007 Feb 8. [Article]
  5. Vermeeren A: Residual effects of hypnotics: epidemiology and clinical implications. CNS Drugs. 2004;18(5):297-328. [Article]
  6. Nordt SP, Clark RF: Midazolam: a review of therapeutic uses and toxicity. J Emerg Med. 1997 May-Jun;15(3):357-65. [Article]
  7. Jembrek MJ, Vlainic J: GABA Receptors: Pharmacological Potential and Pitfalls. Curr Pharm Des. 2015;21(34):4943-59. [Article]
  8. Wheless JW: A critical evaluation of midazolam nasal spray for the treatment of patients with seizure clusters. Expert Rev Neurother. 2021 Nov;21(11):1195-1205. doi: 10.1080/14737175.2021.1890033. Epub 2021 Mar 12. [Article]
  9. Siegel GJ, Agranoff BW, Albers RW et al. (1999). Basic Neurochemistry: Molecular, Cellular and Medical Aspects (6th ed.). Lippincott Williams.
  10. Drug Scheduling: United States Drug Enforcement Administration (DEA) [Link]
  11. DailyMed: Midazolam [Link]
  12. NAYZILAM® (midazolam) nasal spray - FDA Label [Link]
  13. FDA Approved Drug Products: NAYZILAM (midazolam) nasal spray, CIV Jan 2023 [Link]
  14. DailyMed: Midazolam injection [Link]
  15. FDA Approved Drug Products: SEIZALAM® (midazolam injection), for intramuscular use [Link]
  16. EMA Approved Drug Products: BUCCOLAM oromucosal solution [Link]
  17. Health Canada Approved Drug Products: Midazolam Intramuscular or Intravenous Injection (January 2023) [Link]
  18. Midazolam Chemical Handbook [Link]
  19. CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 211321Orig1s000 [Link]
  20. Intravenous Midazolam FDA label [File]
  21. MedSafe NZ: Midazolam Inj [File]
Human Metabolome Database
HMDB0014821
KEGG Drug
D00550
KEGG Compound
C07524
PubChem Compound
4192
PubChem Substance
46507611
ChemSpider
4047
BindingDB
21363
RxNav
6960
ChEBI
6931
ChEMBL
CHEMBL655
ZINC
ZINC000095626706
Therapeutic Targets Database
DAP000241
PharmGKB
PA450496
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
08J
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Midazolam
PDB Entries
3u5k / 5te8
FDA label
Download (250 KB)
MSDS
Download (68.9 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
  • Apothecon inc div bristol myers squibb
  • App pharmaceuticals llc
  • Astrazeneca pharmaceuticals lp
  • Baxter healthcare corp anesthesia and critical care
  • Baxter healthcare corp anesthesia critical care
  • Bedford laboratories div ben venue laboratories inc
  • Ben venue laboratories inc
  • Claris lifesciences ltd
  • Hospira inc
  • International medicated systems ltd
  • International medication systems ltd
  • Taylor pharmaceuticals
  • Wockhardt ltd
  • Hlr technology
  • Apotex inc richmond hill
  • Hi tech pharmacal co inc
  • Paddock laboratories inc
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Hoffmann la roche inc
Packagers
  • Akorn Inc.
  • APP Pharmaceuticals
  • A-S Medication Solutions LLC
  • B&B Pharmaceuticals
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Cardinal Health
  • Cura Pharmaceutical Co. Inc.
  • Dispensing Solutions
  • Ebewe Pharma
  • Hi Tech Pharmacal Co. Inc.
  • Hospira Inc.
  • Mikart Inc.
  • Novex Pharma
  • Paddock Labs
  • Patheon Inc.
  • Pharmedium
  • Physicians Total Care Inc.
  • Ranbaxy Laboratories
  • Roxane Labs
  • Wockhardt Ltd.
Dosage Forms
FormRouteStrength
LiquidIntramuscular; Intravenous1 mg / mL
SolutionIntramuscular; Intravenous1 mg
SolutionBuccal10 mg
SolutionBuccal2.5 mg
SolutionBuccal5 mg
SolutionBuccal7.5 mg
SolutionParenteral16.680 mg
InjectionIntramuscular; Intravenous15 mg/3ml
InjectionIntramuscular; Intravenous50 mg/10ml
InjectionIntramuscular; Intravenous5 mg/5ml
SolutionIntramuscular; Intravenous
Injection, solutionIntramuscular; Intravenous; Rectal
InjectionIntravenous
InjectionIntramuscular; Intravenous15 MG
InjectionIntramuscular; Intravenous5 mg/ml
InjectionIntramuscular; Intravenous5 MG
InjectionIntramuscular; Intravenous
TabletOral10.200 mg
SolutionIntramuscular; Intravenous; Rectal1 mg
Injection, solutionParenteral
SolutionIntravenous5 mg
InjectionIntramuscular; Intravenous; Rectal15 MG/3ML
SolutionIntramuscular; Intravenous; Rectal5 MG/5ML
InjectionIntramuscular; Intravenous; Rectal5 MG/ML
Tablet, film coatedOral15 mg
Tablet, film coatedOral7.5 mg
TabletOral7.5 MG
SolutionIntramuscular; Intravenous; Rectal15 mg
SolutionIntramuscular; Intravenous; Rectal50 mg
SolutionIntramuscular; Intravenous5 mg
SolutionIntramuscular; Intravenous15 mg
SolutionOral2.5 MG
SolutionOral5 MG
SolutionOral7.5 MG
SolutionOral10 mg
Injection, solution
SolutionIntravenous5.000 mg
SolutionParenteral5.0 mg
Injection, solutionIntramuscular; Intravenous; Rectal5 mg
InjectionIntramuscular; Intravenous1 mg/mL
Injection, solutionIntramuscular; Intravenous
Injection, solutionIntramuscular; Intravenous10 mg/2mL
Injection, solutionIntramuscular; Intravenous2 mg/2mL
Injection, solutionIntramuscular; Intravenous5 mg/5mL
SolutionParenteral15 mg
SolutionIntramuscular; Parenteral15 mg
SolutionIntramuscular; Intravenous50 mg
SolutionIntramuscular; Intravenous500000 mg
SolutionIntravenous
Tablet, coatedOral7.5 mg
Injection, solution1 MG/ML
Injection, solutionParenteral; Rectal1 MG/ML
Injection, solutionRectal5 MG/ML
Injection, solutionIntravenous0.5 mg/1mL
Injection, solutionIntravenous1 mg/1mL
InjectionIntramuscular; Intravenous1 mg/1mL
InjectionIntramuscular; Intravenous10 mg/2mL
InjectionIntramuscular; Intravenous2 mg/2mL
InjectionIntramuscular; Intravenous5 mg/1mL
Injection, solutionIntramuscular; Intravenous1 mg/1mL
Injection, solutionIntramuscular; Intravenous5 mg/1mL
SyrupOral10 mg/5mL
SyrupOral2 mg/1mL
Injection, solution5 MG/ML
InjectionIntravenous1 mg/1mL
LiquidIntramuscular; Intravenous5 mg / mL
SolutionIntramuscular; Intravenous1 mg / mL
SolutionIntramuscular; Intravenous5 mg / mL
SolutionIntravenous1 mg / mL
Injection, solutionParenteral1 mg/ml
Solution
Tablet, film coatedOral
Injection, solutionIntramuscular; Intravenous; Rectal1 mg/mL
Injection, solutionIntramuscular; Intravenous; Rectal5 mg/ml
InjectionIntravenous1 mg/ml
InjectionParenteral1 MG/ML
Injection, solutionParenteral2 mg/ml
InjectionIntravenous5 mg/ml
Injection, solutionParenteral5 mg/ml
InjectionParenteral5 MG/ML
SolutionIntravenous50 mg
Injection
Injection, solutionIntravenous5 mg
TrocheSublingual
Injection, solutionIntramuscular10 mg/0.7mL
SprayNasal5 mg/0.1mL
SolutionOral2 MG/ML
SolutionOral
SolutionIntravenous5.60 mg
SolutionParenteral5.000 mg
SolutionIntramuscular; Intravenous; Rectal
Injection, solutionIntramuscular5 mg/1mL
SolutionIntramuscular; Intravenous; Rectal5 mg
SolutionParenteral5.560 mg
SolutionParenteral5.00 mg
SolutionParenteral5.00000 mg
SolutionParenteral16.68 mg
SolutionParenteral15.000 mg
SolutionIntramuscular; Intravenous; Rectal5 mg/mL
SolutionIntramuscular; Intravenous; Rectal1 mg/mL
SolutionIntramuscular5.00 mg
Prices
Unit descriptionCostUnit
Midazolam 5 mg/ml3.9USD ml
Midazolam-nacl 2 mg/ml inj2.31USD ml
Midazolam hcl 5 mg/ml vial1.18USD ml
Midazolam-nacl 1 mg/ml inj1.13USD ml
Midazolam hcl 2 mg/ml syrup1.08USD ml
Midazolam 1 mg/ml isecure syr0.73USD ml
Midazolam hcl 1 mg/ml vial0.26USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9289432No2016-03-222028-01-18US flag
US9687495No2017-06-272028-01-18US flag
US8217033No2012-07-102028-01-18US flag
US8809322No2014-08-192028-01-18US flag
US10966990No2021-04-062038-06-20US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)161-164L45093
boiling point (°C)496.9±55.0L45093
water solubility54mg/LL45093
logP2.73L45093
Predicted Properties
PropertyValueSource
Water Solubility0.00987 mg/mLALOGPS
logP3.89ALOGPS
logP3.97Chemaxon
logS-4.5ALOGPS
pKa (Strongest Basic)6.19Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area30.18 Å2Chemaxon
Rotatable Bond Count1Chemaxon
Refractivity99.43 m3·mol-1Chemaxon
Polarizability32.71 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9724
Caco-2 permeable+0.8866
P-glycoprotein substrateNon-substrate0.5074
P-glycoprotein inhibitor IInhibitor0.5587
P-glycoprotein inhibitor IIInhibitor0.8388
Renal organic cation transporterInhibitor0.7476
CYP450 2C9 substrateNon-substrate0.7366
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7194
CYP450 1A2 substrateInhibitor0.8586
CYP450 2C9 inhibitorInhibitor0.7132
CYP450 2D6 inhibitorNon-inhibitor0.6887
CYP450 2C19 inhibitorInhibitor0.6554
CYP450 3A4 inhibitorNon-inhibitor0.5214
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9001
Ames testNon AMES toxic0.8024
CarcinogenicityNon-carcinogens0.7703
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.1488 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9827
hERG inhibition (predictor II)Non-inhibitor0.7379
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-002g-5092000000-4478c9440e5f31cecc49
Mass Spectrum (Electron Ionization)MSsplash10-03di-3839000000-42781254e15bcd5b31b6
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-03di-0910000000-98021a5812f1663e9397
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0009000000-2411220f611ba30ef225
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0009000000-c724b297ae99edb399d3
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004l-0098000000-b57c162c4eeaad9ef111
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0090000000-a3133528f5491f4c9a6b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-05fs-0290000000-ee126555f849ecfff795
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0009000000-4ae622c7b53369b0cfb1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0019000000-00c3c9e2813a454acda1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-002f-0093000000-a8ca99ef6c84536bff07
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0091000000-3edc4aa6f67d99b789a8
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0abd-0290000000-aa5e16437618ad2adb86
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05fs-0490000000-a323090224c5b01e3990
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0189000000-6e704a4a2a65211394ab
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-0910000000-98021a5812f1663e9397
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0009000000-000181022f4b8c3d9499
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0009000000-9530bcfae2ea7c6b7304
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0009000000-17a8419ced6a72f33e66
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0029000000-af8686767ab034b02afd
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0l4i-0092000000-3d68ea331540f8a06eba
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0umm-0090000000-fa5eb1375abc7482e578
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]-174.5475601
predicted
DarkChem Lite v0.1.0
[M-H]-173.7339
predicted
DeepCCS 1.0 (2019)
[M+H]+175.4209601
predicted
DarkChem Lite v0.1.0
[M+H]+176.09192
predicted
DeepCCS 1.0 (2019)
[M+Na]+174.8217601
predicted
DarkChem Lite v0.1.0
[M+Na]+182.9479
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. 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]
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. 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]
  2. 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]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Potentiator
General Function
Identical protein binding
Specific Function
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name
ADORA2A
Uniprot ID
P29274
Uniprot Name
Adenosine receptor A2a
Molecular Weight
44706.925 Da
References
  1. Seubert CN, Morey TE, Martynyuk AE, Cucchiara RF, Dennis DM: Midazolam selectively potentiates the A(2A) - but not A1- receptor--mediated effects of adenosine: role of nucleoside transport inhibition and clinical implications. Anesthesiology. 2000 Feb;92(2):567-77. doi: 10.1097/00000542-200002000-00041. [Article]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. Foti RS, Rock DA, Wienkers LC, Wahlstrom JL: Selection of alternative CYP3A4 probe substrates for clinical drug interaction studies using in vitro data and in vivo simulation. Drug Metab Dispos. 2010 Jun;38(6):981-7. doi: 10.1124/dmd.110.032094. Epub 2010 Mar 4. [Article]
  2. Pelkonen O, Maenpaa J, Taavitsainen P, Rautio A, Raunio H: Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica. 1998 Dec;28(12):1203-53. [Article]
  3. Zhou S, Chan E, Lim LY, Boelsterli UA, Li SC, Wang J, Zhang Q, Huang M, Xu A: Therapeutic drugs that behave as mechanism-based inhibitors of cytochrome P450 3A4. Curr Drug Metab. 2004 Oct;5(5):415-42. [Article]
  4. Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA: Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002 Aug;30(8):883-91. [Article]
  5. Galetin A, Clarke SE, Houston JB: Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Drug Metab Dispos. 2002 Dec;30(12):1512-22. [Article]
  6. Obach RS, Reed-Hagen AE: Measurement of Michaelis constants for cytochrome P450-mediated biotransformation reactions using a substrate depletion approach. Drug Metab Dispos. 2002 Jul;30(7):831-7. [Article]
  7. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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. Klieber S, Hugla S, Ngo R, Arabeyre-Fabre C, Meunier V, Sadoun F, Fedeli O, Rival M, Bourrie M, Guillou F, Maurel P, Fabre G: Contribution of the N-glucuronidation pathway to the overall in vitro metabolic clearance of midazolam in humans. Drug Metab Dispos. 2008 May;36(5):851-62. doi: 10.1124/dmd.107.019539. Epub 2008 Feb 6. [Article]
  2. Hyland R, Osborne T, Payne A, Kempshall S, Logan YR, Ezzeddine K, Jones B: In vitro and in vivo glucuronidation of midazolam in humans. Br J Clin Pharmacol. 2009 Apr;67(4):445-54. doi: 10.1111/j.1365-2125.2009.03386.x. [Article]
  3. Seo KA, Bae SK, Choi YK, Choi CS, Liu KH, Shin JG: Metabolism of 1'- and 4-hydroxymidazolam by glucuronide conjugation is largely mediated by UDP-glucuronosyltransferases 1A4, 2B4, and 2B7. Drug Metab Dispos. 2010 Nov;38(11):2007-13. doi: 10.1124/dmd.110.035295. Epub 2010 Aug 16. [Article]
  4. Liu Y, She M, Wu Z, Dai R: The inhibition study of human UDP-glucuronosyltransferases with cytochrome P450 selective substrates and inhibitors. J Enzyme Inhib Med Chem. 2011 Jun;26(3):386-93. doi: 10.3109/14756366.2010.518965. Epub 2010 Oct 13. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Patki KC, Von Moltke LL, Greenblatt DJ: In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5. Drug Metab Dispos. 2003 Jul;31(7):938-44. [Article]
  2. Wandel C, Bocker R, Bohrer H, Browne A, Rugheimer E, Martin E: Midazolam is metabolized by at least three different cytochrome P450 enzymes. Br J Anaesth. 1994 Nov;73(5):658-61. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA: Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002 Aug;30(8):883-91. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Klieber S, Hugla S, Ngo R, Arabeyre-Fabre C, Meunier V, Sadoun F, Fedeli O, Rival M, Bourrie M, Guillou F, Maurel P, Fabre G: Contribution of the N-glucuronidation pathway to the overall in vitro metabolic clearance of midazolam in humans. Drug Metab Dispos. 2008 May;36(5):851-62. doi: 10.1124/dmd.107.019539. Epub 2008 Feb 6. [Article]
  2. Swart EL, Slort PR, Plotz FB: Growing up with midazolam in the neonatal and pediatric intensive care. Curr Drug Metab. 2012 Jul;13(6):760-6. doi: 10.2174/138920012800840347. [Article]
  3. Tian DD, Leonowens C, Cox EJ, Gonzalez-Perez V, Frederick KS, Scarlett YV, Fisher MB, Paine MF: Indinavir Increases Midazolam N-Glucuronidation in Humans: Identification of an Alternate CYP3A Inhibitor Using an In Vitro to In Vivo Approach. Drug Metab Dispos. 2019 Jul;47(7):724-731. doi: 10.1124/dmd.119.087007. Epub 2019 Apr 26. [Article]
  4. Hyland R, Osborne T, Payne A, Kempshall S, Logan YR, Ezzeddine K, Jones B: In vitro and in vivo glucuronidation of midazolam in humans. Br J Clin Pharmacol. 2009 Apr;67(4):445-54. doi: 10.1111/j.1365-2125.2009.03386.x. [Article]
  5. Nguyen HQ, Kimoto E, Callegari E, Obach RS: Mechanistic Modeling to Predict Midazolam Metabolite Exposure from In Vitro Data. Drug Metab Dispos. 2016 May;44(5):781-91. doi: 10.1124/dmd.115.068601. Epub 2016 Mar 8. [Article]
  6. Wessels AMA, Bolhuis MS, Bult W, Nijsten MWN, Kneyber MCJ, Touw DJ: A fast and simple method for the simultaneous analysis of midazolam, 1-hydroxymidazolam, 4-hydroxymidazolam and 1-hydroxymidazolam glucuronide in human serum, plasma and urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Jan 1;1162:122476. doi: 10.1016/j.jchromb.2020.122476. Epub 2020 Dec 3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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. Klieber S, Hugla S, Ngo R, Arabeyre-Fabre C, Meunier V, Sadoun F, Fedeli O, Rival M, Bourrie M, Guillou F, Maurel P, Fabre G: Contribution of the N-glucuronidation pathway to the overall in vitro metabolic clearance of midazolam in humans. Drug Metab Dispos. 2008 May;36(5):851-62. doi: 10.1124/dmd.107.019539. Epub 2008 Feb 6. [Article]
  2. Swart EL, Slort PR, Plotz FB: Growing up with midazolam in the neonatal and pediatric intensive care. Curr Drug Metab. 2012 Jul;13(6):760-6. doi: 10.2174/138920012800840347. [Article]
  3. Tian DD, Leonowens C, Cox EJ, Gonzalez-Perez V, Frederick KS, Scarlett YV, Fisher MB, Paine MF: Indinavir Increases Midazolam N-Glucuronidation in Humans: Identification of an Alternate CYP3A Inhibitor Using an In Vitro to In Vivo Approach. Drug Metab Dispos. 2019 Jul;47(7):724-731. doi: 10.1124/dmd.119.087007. Epub 2019 Apr 26. [Article]
  4. Hyland R, Osborne T, Payne A, Kempshall S, Logan YR, Ezzeddine K, Jones B: In vitro and in vivo glucuronidation of midazolam in humans. Br J Clin Pharmacol. 2009 Apr;67(4):445-54. doi: 10.1111/j.1365-2125.2009.03386.x. [Article]
  5. Nguyen HQ, Kimoto E, Callegari E, Obach RS: Mechanistic Modeling to Predict Midazolam Metabolite Exposure from In Vitro Data. Drug Metab Dispos. 2016 May;44(5):781-91. doi: 10.1124/dmd.115.068601. Epub 2016 Mar 8. [Article]
  6. Wessels AMA, Bolhuis MS, Bult W, Nijsten MWN, Kneyber MCJ, Touw DJ: A fast and simple method for the simultaneous analysis of midazolam, 1-hydroxymidazolam, 4-hydroxymidazolam and 1-hydroxymidazolam glucuronide in human serum, plasma and urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Jan 1;1162:122476. doi: 10.1016/j.jchromb.2020.122476. Epub 2020 Dec 3. [Article]

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. Influence of midazolam on the protein binding of ketorolac [Link]
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. Influence of midazolam on the protein binding of ketorolac [Link]

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. Tolle-Sander S, Rautio J, Wring S, Polli JW, Polli JE: Midazolam exhibits characteristics of a highly permeable P-glycoprotein substrate. Pharm Res. 2003 May;20(5):757-64. doi: 10.1023/a:1023433502647. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium:dicarboxylate symporter activity
Specific Function
Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport ...
Gene Name
SLC1A2
Uniprot ID
P43004
Uniprot Name
Excitatory amino acid transporter 2
Molecular Weight
62103.665 Da
References
  1. Sakai F, Amaha K: Midazolam and ketamine inhibit glutamate release via a cloned human brain glutamate transporter. Can J Anaesth. 2000 Aug;47(8):800-6. doi: 10.1007/BF03019485. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 29, 2024 22:51