Effect of Hepatic Impairment on Cobimetinib Pharmacokinetics: The Complex Interplay Between Physiological Changes and Drug Characteristics.
Child-Pugh classification
cobimetinib
hepatic impairment
pharmacokinetics
protein binding
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:
02 2021
02 2021
Historique:
received:
15
01
2020
accepted:
07
06
2020
pubmed:
23
7
2020
medline:
15
12
2021
entrez:
23
7
2020
Statut:
ppublish
Résumé
Cobimetinib is a kinase inhibitor indicated for use in combination with vemurafenib for treatment of unresectable/metastatic melanoma with specific BRAF mutations. Cobimetinib is extensively metabolized in liver; thus, patients with hepatic impairment (HI) might have increased cobimetinib exposure. In this study, we investigated the impact of HI on the pharmacokinetics (PK) and safety of cobimetinib. Subjects with normal hepatic function and mild to severe HI were enrolled. All subjects received a single oral dose of 10 mg cobimetinib, and serial blood samples were collected at specified times. Cobimetinib PK in subjects with mild and moderate HI was similar to that in those with normal liver function. However, subjects with severe HI, on average, showed ∼30% lower total AUC
Identifiants
pubmed: 32696585
doi: 10.1002/cpdd.847
pmc: PMC7891419
doi:
Substances chimiques
Antineoplastic Agents
0
Azetidines
0
Piperidines
0
Protein Kinase Inhibitors
0
cobimetinib
ER29L26N1X
Types de publication
Controlled Clinical Trial
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
144-152Informations de copyright
© 2020 Genentech, Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.
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