[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.
