Amenamevir: Studies of Potential CYP3A-Mediated Pharmacokinetic Interactions With Midazolam, Cyclosporine, and Ritonavir in Healthy Volunteers.
Clin Pharmacol Drug Dev
; 7(8): 844-859, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-30044899
Amenamevir (formerly ASP2151) is a helicase-primase inhibitor being developed for the treatment of herpesvirus infection. Amenamevir is both a substrate and inducer of cytochrome P450 (CYP) 3A4. Three studies were done in healthy volunteers to investigate potential CYP3A pharmacokinetic interactions with the following drugs: (1) Midazolam (probe substrate for CYP3A): After 10 days' pretreatment with amenamevir 400 mg daily, geometric mean maximum concentration of drug in blood plasma (Cmax ) and area under the plasma drug concentration-time curve from time zero to infinity (AUC0-∞ ) of midazolam 7.5 mg were about 68% and 51%, respectively, of those after midazolam alone. (2) Cyclosporine (substrate and inhibitor of CYP3A): After 5 days' pretreatment with cyclosporine 100 mg twice daily, geometric mean Cmax of amenamevir after 400-mg and 1200-mg single doses was, respectively, about 66% and 69%, and AUC0-∞ about 82% and 79%, of those after amenamevir alone. (3) Ritonavir (inhibitor of CYP3A): When given with single doses of ritonavir 600 mg, geometric mean Cmax of amenamevir after 400-mg and 1200-mg single doses was, respectively, about 1.4 and 1.6 times higher, and geometric mean AUC0-∞ about 2.6 and 3.3 times higher, than after amenamevir alone. Amenamevir has the potential to be involved in CYP3A-mediated pharmacokinetic interactions in clinical practice.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxidiazóis
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Midazolam
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Ciclosporina
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Ritonavir
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Citocromo P-450 CYP3A
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Pharmacol Drug Dev
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Reino Unido