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


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).


METHODS
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.
Derks
Michael
M
Department of Clinical Pharmacology, F. Hoffmann-La Roche Ltd, Basel, Switzerland. michael.derks@roche.com
Abt
Markus
M
Parr
Graeme
G
Meneses-Lorente
Georgina
G
Young
Anne-Marie
AM
Phelan
Mary
M
D000328:Adult; D000577:Amides; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000069059:Atorvastatin; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004952:Esters; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D013438:Sulfhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
D000577:Amides; D000924:Anticholesteremic Agents; D004952:Esters; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D013438:Sulfhydryl Compounds; C411602:dalcetrapib; D000069059:Atorvastatin