Rosuvastatin raises its own peak concentration by 26 percent when combined with dalcetrapib, but the LDL benefit of the combination still exceeds statin alone (J Clin Pharmacol 2010)

Dalcetrapib targets cholesteryl ester transfer protein and increases high-density lipoprotein cholesterol (HDL-C) levels. It is in clinical development for the prevention of cardiovascular events and will likely be used in combination with standard of care, including statins. Three crossover studies in healthy males investigated the pharmacokinetic drug-drug interaction potential of 900 mg dalcetrapib and statins: two 3-period studies (dalcetrapib plus pravastatin or rosuvastatin) and a 2-period study (dalcetrapib plus simvastatin). Effect on lipids and safety were secondary end points. The 900 mg dose investigated is higher than the 600 mg dose currently being investigated in Phase III. Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin was not associated with significant increases in statin exposure except for a 26% increase in rosuvastatin C(max) (90% CI 1.088 to 1.468) but not AUC(0-24) (90% CI 0.931 to 1.085). Dalcetrapib AUC(0-24) and C(max) were not significantly altered by coadministration with pravastatin, and were significantly lower when dalcetrapib was coadministered with rosuvastatin or simvastatin compared with dalcetrapib alone. The HDL-C increase with dalcetrapib was not compromised by coadministration with statins, and reduction in low-density lipoprotein cholesterol with dalcetrapib coadministered with statins was greater than with statins alone. Dalcetrapib alone and coadministered with statins was generally well tolerated.