No clinically relevant drug-drug interactions when dalcetrapib is co-administered with atorvastatin.

摘要

OBJECTIVES: Dalcetrapib, which targets cholesteryl ester transfer protein, is in clinical development for prevention of cardiovascular events and is likely to be used concomitantly with statins. Two studies investigated co-administration of dalcetrapib with atorvastatin and any effects of the timing of atorvastatin on the pharmacokinetics of dalcetrapib. RESEARCH DESIGN AND METHODS: Two crossover studies were performed in healthy subjects: a two-period study of dalcetrapib 900 mg concurrently with atorvastatin (concurrent dosing study) and a three-period study of dalcetrapib 600 mg (dose chosen for Phase III) with atorvastatin concurrently or serially 4 h after dalcetrapib (interval dosing study). Main outcome measures: The primary pharmacokinetic end points were AUC(0 - 24) and C(max); lipid effects and tolerability were secondary end points. RESULTS: In the concurrent study (n = 26), co-administration reduced dalcetrapib AUC(0 - 24) and C(max) and caused small changes in AUC(0 - 24) and C(max) of atorvastatin and its active metabolites. In the interval study (n = 52), serial and concurrent co-administration of atorvastatin resulted in similar reductions in dalcetrapib exposure that were comparable to those observed in the concurrent dosing study. Co-administration did not decrease the efficacy of dalcetrapib or atorvastatin and was generally well tolerated. CONCLUSIONS: These results indicate no clinically relevant interactions for co-administration of dalcetrapib with atorvastatin.