Explore a selection of our essential drug information below, or:
Identification
- Summary
Abametapir is a pediculicide metalloproteinase used topically in the treatment of head lice infection.
- Brand Names
- Xeglyze
- Generic Name
- Abametapir
- DrugBank Accession Number
- DB11932
- Background
Abametapir is a novel pediculicidal metalloproteinase inhibitor used to treat infestations of head lice.4 The life cycle of head lice (Pediculus capitis) is approximately 30 days, seven to twelve of which are spent as eggs laid on hair shafts near the scalp.2 Topical pediculicides generally lack adequate ovicidal activity,2 including standard-of-care treatments such as permethrin, and many require a second administration 7-10 days following the first to kill newly hatched lice that resisted the initial treatment. The necessity for follow-up treatment may lead to challenges with patient adherence, and resistance to agents like permethrin and pyrethrins/piperonyl butoxide may be significant in some areas.3
Investigations into novel ovicidal treatments revealed that several metalloproteinase enzymes were critical to the egg hatching and survival of head lice, and these enzymes were therefore identified as a potential therapeutic target.1 Abemetapir is an inhibitor of these metalloproteinase enzymes, and the first topical pediculicide to take advantage of this novel target. The improved ovicidal activity (90-100% in vitro) of abemetapir allows for a single administration, in contrast to many other topical treatments, and its novel and relatively non-specific mechanism may help to curb the development of resistance to this agent.1
Abametapir was first approved for use in the United States under the brand name Xeglyze on July 27, 2020.6
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Abametapir (DB11932)
- Weight
- Average: 184.242
Monoisotopic: 184.100048394 - Chemical Formula
- C12H12N2
- Synonyms
- 5,5'-Dimethyl-2,2'-bipyridine
- 5,5'-Dimethyl-2,2'-dipyridyl
- Abametapir
- External IDs
- BRN 0123183
- HA 44
- HA-44
- HA44
Pharmacology
- Indication
Abametapir is indicated, in the context of an overall lice management program, for the topical treatment of head lice infestation in patients 6 months of age and older.4
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Head lice infestation •••••••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Abametavir has been shown to inhibit all stages of embryo development in both head and body lice1 by interfering with enzymes critical to this process. It is relatively unique amongst lice treatments in that it requires only a single application, whereas many current therapies require two applications, due to its exceptional potency and unique mechanism.1,4 Its predominant metabolite, abametapir carboxyl, has a prolonged residence time in the body, with an estimated half-life of 71 ± 40 hours or longer in adults - as this metabolite has been shown to inhibit cytochrome P450 enzymes in vitro, the use of substrates of CYP3A4, CYP2B6, or CYP1A2 should be avoided for two weeks following the administration of abametapir.4
Abametapir lotion is formulated with benzyl alcohol, which has been associated with significant toxicity following unintentional systemic exposure, particularly in neonates and low birth weight infants.4 Benzyl alcohol-containing formulations should not be administered to patients <6 months of age, and should be administered to pediatric patients cautiously and under direct supervision of an adult to mitigate the risk of unintentional oral ingestion.4
- Mechanism of action
There are several metalloproteinases (enzymes requiring metal co-factors to function)1 involved in the process of louse egg hatching and survival.2,4 In vitro studies have demonstrated that metal-chelating agents can inhibit the activity of these proteins,2 and may therefore be valuable pediculicidal agents.
Abametapir is a metalloproteinase inhibitor that targets louse metalloproteinases which are critical to their development and hatching.4,2
- Absorption
In a pharmacokinetic trial with both adult and pediatric patients, the Cmax and AUC0-8h in the adult group were 41 ng/mL and 121 ng.h/mL and the Cmax and AUC0-8h in the pediatric group were 73 ng/mL and 264 ng.h/mL.4 In general, systemic exposure to abametapir appears to decrease with increasing age.4 The median Tmax of abemetapir is 0.57 - 1.54 hours.4
Following topical administration, benzyl alcohol was found in detectable quantities in the serum of 7 out of 39 pediatric patients. The Cmax of benzyl alcohol in these subjects ranged from 0.52 to 3.57 μg/mL.4
The predominant circulating metabolite of abemetapir (abemtapir carboxylate) is eliminated slowly from the circulation and is therefore found at higher serum concentrations than its parent drug - based on data collected for 72 hours post-administration, the ratios of serum Cmax and AUC0-72h between abametapir and abametapir carboxylate were approximately 30 and 250, respectively.4
- Volume of distribution
Data regarding the volume of distribution of abametapir are not available.
- Protein binding
Both abametapir and abametapir carboxyl are high protein-bound in plasma, although the specific proteins to which they bind are unclear.4 Following topical administration, abametapir is 91.3-92.3% protein-bound and abametapir carboxyl is 96.0-97.5% protein-bound.4
- Metabolism
The biotransformation of abametapir is extensive and primarily mediated by CYP1A2. It is metabolized first to abametapir hydroxyl and then further to abametapir carboxyl - the latter is cleared slowly from the plasma, resulting in higher systemic concentrations than that of the parent drug.4 In vitro studies suggest that abametapir carboxyl may act as an inhibitor of CYP3A4, CYP2B6, and CYP1A2, particularly at the relatively high and prolonged concentrations observed following topical administration of abametapir.4
Hover over products below to view reaction partners
- Route of elimination
The clearance and excretion of abametapir has not been examined in patients.4
- Half-life
The elimination half-lives of abametapir and its metabolites have not been well-characterized, but the estimated half-life of abametapir carboxyl is 71 ± 40 hours (or longer) in adults.4
- Clearance
The clearance and excretion of abametapir has not been examined in patients.4
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The intraperitoneal LD50 of abametapir in mice is 225 mg/kg.5 Topical formulations of abametapir contain benzyl alcohol, which has been associated with fatal reactions including "gasping syndrome" following systemic exposure in neonates and low birth weight infants. The use of benzyl alcohol-containing abametapir formulations should be avoided in patients <6 months of age due to an increased risk of unintentional systemic absorption.4 As benzyl alcohol toxicity may also occur in pediatric patients following accidental oral ingestion, the manufacturer recommends that it be administered to pediatric patients only under the direct supervision of adult.4 Symptoms of benzyl alcohol toxicity may include significant gastrointestinal and central nervous system adverse effects, with severe cases leading to respiratory depression and death.4 If toxicity is expected, patients should be advised to contact their nearest poison control center.
The minimal amount of benzyl alcohol at which toxicity might occur is unclear. Toxicity is more likely in premature infants, low birth weight infants, and those receiving high doses.4
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The serum concentration of 1,2-Benzodiazepine can be increased when it is combined with Abametapir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Abametapir. Abiraterone The serum concentration of Abiraterone can be increased when it is combined with Abametapir. Acalabrutinib The serum concentration of Acalabrutinib can be increased when it is combined with Abametapir. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Abametapir. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Xeglyze
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Xeglyze Lotion 0.74 g/100g Topical Dr. Reddy's Laboratories Inc. 2021-01-29 Not applicable US 
Categories
- ATC Codes
- P03AX07 — Abametapir
- Drug Categories
- Antiparasitic Products, Insecticides and Repellents
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Ectoparasiticides, Incl. Scabicides
- Ectoparasiticides, Incl. Scabicides, Insecticides and Repellents
- Matrix Metalloproteinase Inhibitors
- Pediculicides
- Pyridines
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as bipyridines and oligopyridines. These are organic compounds containing two pyridine rings linked to each other.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyridines and derivatives
- Sub Class
- Bipyridines and oligopyridines
- Direct Parent
- Bipyridines and oligopyridines
- Alternative Parents
- Methylpyridines / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Hydrocarbon derivatives
- Substituents
- Aromatic heteromonocyclic compound / Azacycle / Bipyridine / Heteroaromatic compound / Hydrocarbon derivative / Methylpyridine / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Pediculus humanus
Chemical Identifiers
- UNII
- 6UO390AMFB
- CAS number
- 1762-34-1
- InChI Key
- PTRATZCAGVBFIQ-UHFFFAOYSA-N
- InChI
- InChI=1S/C12H12N2/c1-9-3-5-11(13-7-9)12-6-4-10(2)8-14-12/h3-8H,1-2H3
- IUPAC Name
- 5,5'-dimethyl-2,2'-bipyridine
- SMILES
- CC1=CC=C(N=C1)C1=CC=C(C)C=N1
References
- Synthesis Reference
Ronald Harding, Lewis David Schulz, Vernon Morrison Bowles, "Pediculicidal composition." WIPO Patent WO2015107384A2, published July, 2015.
- General References
- Bowles VM, Yoon KS, Barker SC, Tran C, Rhodes C, Clark MJ: Ovicidal Efficacy of Abametapir Against Eggs of Human Head and Body Lice (Anoplura: Pediculidae). J Med Entomol. 2017 Jan;54(1):167-172. doi: 10.1093/jme/tjw132. Epub 2016 Aug 21. [Article]
- Bowles VM, Hanegraaf S, Ahveninen T, Sidgiddi S, Allenby K, Alsop H: Effect of a New Head Lice Treatment, Abametapir Lotion, 0.74%, on Louse Eggs: A Randomized, Double-Blind Study. Glob Pediatr Health. 2019 Feb 22;6:2333794X19831295. doi: 10.1177/2333794X19831295. eCollection 2019. [Article]
- Gunning K, Kiraly B, Pippitt K: Lice and Scabies: Treatment Update. Am Fam Physician. 2019 May 15;99(10):635-642. [Article]
- FDA Approved Drug Products: Xeglyze (Abametapir) topical lotion [Link]
- BioVision: Abametapir SDS [Link]
- BusinessWire: Dr. Reddy's Laboratories received approval of XEGLYZE™ (abametapir) lotion, 0.74%, in the U.S. [Link]
- External Links
- PubChem Compound
- 15664
- PubChem Substance
- 347828259
- ChemSpider
- 14899
- BindingDB
- 50401351
- 2475532
- ChEMBL
- CHEMBL2205807
- ZINC
- ZINC000000403335
- PDBe Ligand
- EI3
- Wikipedia
- Abametapir
- PDB Entries
- 5arb / 5arc / 5ard
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Head Lice Infestation 2 somestatus stop reason just information to hide 2 Completed Treatment Head Lice Infestation 3 somestatus stop reason just information to hide 2 Completed Treatment Lice Infestations 1 somestatus stop reason just information to hide 1 Completed Treatment Head Lice Infestation 2 somestatus stop reason just information to hide 1 Completed Treatment Lice Infestations 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Lotion Topical 0.74 g/100g - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7812163 No 2010-10-12 2026-10-28 US US9839631 No 2017-12-12 2024-07-16 US US8212038 No 2012-07-03 2024-07-16 US US10292389 No 2019-05-21 2034-12-17 US US9357783 No 2016-06-07 2024-07-16 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.98 mg/mL ALOGPS logP 2.43 ALOGPS logP 2.98 Chemaxon logS -2.3 ALOGPS pKa (Strongest Basic) 3.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 25.78 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 56.22 m3·mol-1 Chemaxon Polarizability 21.31 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 150.4894245 predictedDarkChem Lite v0.1.0 [M-H]- 141.07545 predictedDeepCCS 1.0 (2019) [M+H]+ 151.2277245 predictedDarkChem Lite v0.1.0 [M+H]+ 143.47102 predictedDeepCCS 1.0 (2019) [M+Na]+ 150.7710245 predictedDarkChem Lite v0.1.0 [M+Na]+ 150.35585 predictedDeepCCS 1.0 (2019)
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- FDA Approved Drug Products: Xeglyze (Abametapir) topical lotion [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: Xeglyze (Abametapir) topical lotion [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- FDA Approved Drug Products: Xeglyze (Abametapir) topical lotion [Link]
Drug created at October 20, 2016 21:01 / Updated at February 21, 2021 18:53