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JOURNAL ARTICLE
REVIEW
Pharmacokinetic drug evaluation of anacetrapib for the treatment of dyslipidemia.
Expert Opinion on Drug Metabolism & Toxicology 2017 Februrary
INTRODUCTION: While some cholesteryl ester transfer protein inhibitors have had their clinical study interrupted because of no or adverse effects on cardiovascular disease, anacetrapib (MK-0859) is being evaluated in Phase III cardiovascular outcomes trials. We review its pharmacokinetic properties. Areas covered: The apparent anacetrapib terminal elimination half-life after a single dose is 9-62 h in the fasted state and 42-83 h in the fed state. After repeat administrations, a biphasic elimination profile with a long terminal elimination phase (~60-80 h) was observed, although the effective half-life was ~20 h. The steady state appeared to be reached after ~7 days of dosing with 0.85- to 2.8-fold accumulation for AUC0-24 and Cmax, respectively. The unchanged drug is mainly eliminated with feces; renal impairment does not seem be a limitation to the use of the drug. However, liver impairment could cause an increase in the anacetrapib level, especially when associated with CYP3A4 inhibitors, since it is a moderately sensitive CYP3A substrate. Expert opinion: Given the interesting pharmacokinetic profile, and if the preliminary data on cardiovascular outcomes is confirmed, anacetrapib could find a relevant role as a moderately expensive drug between standard lipid-lowering treatment and the new expensive PCKS9 inhibitors.
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