Journal
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
Volume 13, Issue 2, Pages 205-209Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/17425255.2017.1262347
Keywords
Anacetrapib; half-life; metabolism; pharmacological interaction; pharmacokinetics
Ask authors/readers for more resources
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 (similar to 60-80h) was observed, although the effective half-life was similar to 20h. The steady state appeared to be reached after similar to 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available