No pharmacokinetic or pharmacodynamic interaction between atorvastatin and the oral direct thrombin inhibitor ximelagatran.
In this randomized, 2-way crossover study, the potential for interaction was investigated between atorvastatin and ximelagatran, an oral direct thrombin inhibitor. Healthy female and male volunteers (n = 16) received atorvastatin 40 mg as a single oral dose and, in a separate study period, ximelagatran 36 mg twice daily for 5 days plus a 40-mg oral dose of atorvastatin on the morning of day 4. In the 15 subjects completing the study, no pharmacokinetic interaction was detected between atorvastatin and ximelagatran for all parameters investigated, including melagatran (the active form of ximelagatran) area under the plasma concentration versus time curve (AUC) and maximum plasma concentration, atorvastatin acid AUC, and AUC of active 3-hydroxy-3-methyl-glutaryl-coenzyme-A (HMG-CoA) reductase inhibitors. Atorvastatin did not alter the melagatran-induced prolongation of the activated partial thromboplastin time, and both drugs were well tolerated when administered in combination. In conclusion, no pharmacokinetic or pharmacodynamic interaction between atorvastatin and ximelagatran was observed in this study.
Sarich
Troy C
TC
Experimental Medicine, AstraZeneca LP, C4C-123, P.O. Box 15437, 1800 Concord Pike, Wilmington, DE 19850, USA.
Schützer
Kajs-Marie
KM
Dorani
Hassan
H
Wall
Ulrika
U
Kalies
Inge
I
Ohlsson
Lis
L
Eriksson
Ulf G
UG
D000284:Administration, Oral; D000328:Adult; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D000069059:Atorvastatin; D001384:Azetidines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001596:Benzylamines; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000097:blood; D006207:Half-Life; D006538:Heptanoic Acids / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood; D008297:Male; D010314:Partial Thromboplastin Time; D011355:Prodrugs / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011758:Pyrroles / Q000493:pharmacokinetics* / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D004338:Drug Combinations; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011355:Prodrugs; D011758:Pyrroles; C109573:melagatran; C426686:ximelagatran; D000069059:Atorvastatin; D005998:Glycine