Evaluation of the CYP3A and CYP2B6 Drug-Drug Interaction Potential of Lemborexant.
Adult
Area Under Curve
Cytochrome P-450 CYP2B6
/ drug effects
Cytochrome P-450 CYP3A
/ drug effects
Cytochrome P-450 CYP3A Inhibitors
/ pharmacology
Cytochrome P-450 Enzyme Inducers
/ pharmacology
Drug Interactions
Female
Humans
Male
Middle Aged
Orexin Receptor Antagonists
/ administration & dosage
Pyridines
/ administration & dosage
Pyrimidines
/ administration & dosage
Young Adult
CYP2B6
CYP3A
drug-drug interaction
lemborexant
orexin receptor antagonists
pharmacokinetics
Journal
Clinical pharmacology in drug development
ISSN: 2160-7648
Titre abrégé: Clin Pharmacol Drug Dev
Pays: United States
ID NLM: 101572899
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
26
07
2020
accepted:
21
12
2020
pubmed:
18
1
2021
medline:
28
1
2022
entrez:
17
1
2021
Statut:
ppublish
Résumé
Lemborexant is approved for treating insomnia and is under investigation for treating irregular sleep-wake rhythm disorder. Based on in vitro drug-drug interaction (DDI) characteristics, phase 1, open-label DDI studies were conducted to evaluate lemborexant's cytochrome P450 3A (CYP3A) and CYP2B6 interaction potential. Interactions between lemborexant 10 mg and strong and moderate CYP3A inhibitors (itraconazole and fluconazole), a strong CYP3A inducer (rifampin), and CYP3A (midazolam) and CYP2B6 substrates (bupropion) were evaluated. Coadministration of lemborexant with itraconazole or fluconazole resulted in 1.4- to 1.6-fold and 3.7- to 4-fold increases in lemborexant maximum observed concentration (C
Identifiants
pubmed: 33455055
doi: 10.1002/cpdd.915
pmc: PMC8248323
doi:
Substances chimiques
Cytochrome P-450 CYP3A Inhibitors
0
Cytochrome P-450 Enzyme Inducers
0
Orexin Receptor Antagonists
0
Pyridines
0
Pyrimidines
0
lemborexant
0K5743G68X
CYP2B6 protein, human
EC 1.14.14.1
CYP3A protein, human
EC 1.14.14.1
Cytochrome P-450 CYP2B6
EC 1.14.14.1
Cytochrome P-450 CYP3A
EC 1.14.14.1
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
681-690Informations de copyright
© 2021 Eisai Co., Ltd. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.
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