Lack of an effect of anacetrapib on the pharmacokinetics of digoxin in healthy subjects.
Anacetrapib is currently being developed for the oral treatment of dyslipidemia. A clinical study was conducted in healthy subjects to assess the potential for an interaction with orally administered digoxin. Anacetrapib was generally well tolerated when co-administered with digoxin in the healthy subjects in this study. The geometric mean ratios (GMR) for (digoxin + anacetrapib/digoxin alone) and 90% confidence intervals (CIs) for digoxin AUC(0-last) and AUC(0-∞) were 1.05 (0.96, 1.15) and 1.07 (0.98, 1.17), respectively, both being contained in the accepted interval of bioequivalence (0.80, 1.25), the primary hypothesis of the study. The GMR (digoxin + anacetrapib /digoxin alone) and 90% CIs for digoxin C(max) were 1.23 (1.14, 1.32). Median T(max) and mean apparent terminal t(½) of digoxin were comparable between the two treatments. The single-dose pharmacokinetics of orally administered digoxin were not meaningfully affected by multiple-dose administration of anacetrapib, indicating that anacetrapib does not meaningfully inhibit P-glycoprotein. Thus, no dosage adjustment for digoxin is necessary when co-administered with anacetrapib.
Merck & Co., Inc., Whitehouse Station, NJ, USA. rajesh_krishna@merck.com
Rajesh
R
Krishna
Daria
D
Stypinski
Melissa
M
Ali
Amit
A
Garg
Isaias Noel
IN
Gendrano
Andrea
A
Maes
Bruce
B
DeGroot
Yang
Y
Liu
Susie
S
Li
Sandra M
SM
Connolly
John A
JA
Wagner
S Aubrey
SA
Stoch
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage*; D055815:Young Adult
D002316:Cardiotonic Agents; D053480:Cholesterol Ester Transfer Proteins; D004338:Drug Combinations; D023303:Oxazolidinones; D004077:Digoxin; C530884:anacetrapib