title: Pharmacokinetic drug evaluation of anacetrapib for the treatment of dyslipidemia.
abstract: 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.
authors.affiliation: a Medical and Surgical Sciences Dept. , University of Bologna , Bologna , Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Borghi
authors.affiliation: a Medical and Surgical Sciences Dept. , University of Bologna , Bologna , Italy.
authors.forename: Arrigo F G
authors.initials: AF
authors.lastname: Cicero
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D050171:Dyslipidemias / Q000188:drug therapy*; D006207:Half-Life; D006801:Humans; D008107:Liver Diseases / Q000150:complications; D023303:Oxazolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000924:Anticholesteremic Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D023303:Oxazolidinones; C530884:anacetrapib
keywords: Anacetrapib; half-life; metabolism; pharmacokinetics; pharmacological interaction