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.
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No clinically relevant drug-drug interactions when dalcetrapib is co-administered with atorvastatin.
Expert Opin Investig Drugs
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Department of Clinical Pharmacology, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
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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).
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