dc.contributor.author | Adeloye, T | en_US |
dc.contributor.author | Sahgal, O | en_US |
dc.contributor.author | Puri, A | en_US |
dc.contributor.author | Warrington, S | en_US |
dc.contributor.author | Endo, T | en_US |
dc.contributor.author | Dennison, J | en_US |
dc.contributor.author | Johnston, A | en_US |
dc.date.accessioned | 2018-09-20T10:55:34Z | |
dc.date.available | 2018-05-18 | en_US |
dc.date.issued | 2018-11 | en_US |
dc.date.submitted | 2018-09-10T15:59:27.814Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/44827 | |
dc.description.abstract | 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. | en_US |
dc.description.sponsorship | Maruho | en_US |
dc.format.extent | 844 - 859 | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Clin Pharmacol Drug Dev | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. | |
dc.subject | amenamevir | en_US |
dc.subject | cyclosporine | en_US |
dc.subject | drug-drug interaction | en_US |
dc.subject | midazolam | en_US |
dc.subject | ritonavir | en_US |
dc.subject | Adolescent | en_US |
dc.subject | Adult | en_US |
dc.subject | Cyclosporine | en_US |
dc.subject | Cytochrome P-450 CYP3A | en_US |
dc.subject | Cytochrome P-450 CYP3A Inducers | en_US |
dc.subject | Cytochrome P-450 CYP3A Inhibitors | en_US |
dc.subject | Drug Interactions | en_US |
dc.subject | Healthy Volunteers | en_US |
dc.subject | Humans | en_US |
dc.subject | Male | en_US |
dc.subject | Midazolam | en_US |
dc.subject | Middle Aged | en_US |
dc.subject | Oxadiazoles | en_US |
dc.subject | Ritonavir | en_US |
dc.subject | Young Adult | en_US |
dc.title | Amenamevir: Studies of Potential CYP3A-Mediated Pharmacokinetic Interactions With Midazolam, Cyclosporine, and Ritonavir in Healthy Volunteers. | en_US |
dc.type | Article | |
dc.rights.holder | © 2018 The Authors. | |
dc.identifier.doi | 10.1002/cpdd.586 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/30044899 | en_US |
pubs.issue | 8 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 7 | en_US |
dcterms.dateAccepted | 2018-05-18 | en_US |