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Influence of renal and hepatic impairment on the pharmacokinetics of anacetrapib
Author(s) -
Lauring Brett,
Li Xiujiang Susie,
Liu Yang,
Corr Christy,
Lazarus Nicole,
Cote Josee,
Larson Patrick,
Levonas Amy O. Johnson,
Lasseter Kenneth C.,
Preston Richard A.,
Smith William B.,
Lai Eseng,
Wagner John A.
Publication year - 2014
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.320
Subject(s) - pharmacokinetics , medicine , pharmacology , intensive care medicine
Two open‐label, parallel‐group studies evaluated the influence of renal and hepatic insufficiency on the pharmacokinetics of a single‐dose anacetrapib 100 mg. Eligible participants included adult men and women with moderate hepatic impairment (assessed by Child–Pugh criteria) or severe renal impairment (CrCl <30 mL/min/1.73 m 2 ). In both studies, patients were matched (race, age, sex, BMI) with healthy control subjects. Twenty‐four subjects were randomized in each study (12 with either moderate hepatic or severe renal impairment and 12 matched healthy controls). In the hepatic insufficiency study, the geometric mean ratio (GMR; mean value for the group with moderate hepatic insufficiency/mean value for the healthy controls) and 90% CIs for the area under the concentration–time curve from time zero to infinity (AUC 0–∞ ) and the maximum concentration of drug in plasma (C max ) were 1.16 (0.84, 1.60) and 1.02 (0.71, 1.49), respectively. In the renal insufficiency study, the GMRs (mean value for the group with severe renal insufficiency/mean value for the healthy controls) and 90% CIs for AUC 0–∞ and C max were 1.14 (0.80, 1.63) and 1.31 (0.93, 1.83), respectively. Anacetrapib was generally well tolerated and there was no clinically meaningful effect of moderate hepatic or severe renal insufficiency on the pharmacokinetics of anacetrapib.