title: No clinically relevant drug-drug interactions when dalcetrapib is co-administered with atorvastatin.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, F. Hoffmann-La Roche Ltd, Basel, Switzerland. michael.derks@roche.com
authors.forename: Michael
authors.initials: M
authors.lastname: Derks
authors.forename: Markus
authors.initials: M
authors.lastname: Abt
authors.forename: Graeme
authors.initials: G
authors.lastname: Parr
authors.forename: Georgina
authors.initials: G
authors.lastname: Meneses-Lorente
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Young
authors.forename: Mary
authors.initials: M
authors.lastname: Phelan
mesh_terms: 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
chemical_list: 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