Pharmacokinetic drug evaluation of anacetrapib for the treatment of dyslipidemia

ABSTRACT

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.

KEYWORDS:

• Anacetrapib
• half-life
• metabolism
• pharmacological interaction
• pharmacokinetics

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.