Lack of interaction between meloxicam and warfarin in healthy volunteers.
OBJECTIVE
The effect of multiple oral doses of meloxicam 15 mg on the pharmacodynamics and pharmacokinetics of warfarin was investigated in healthy male volunteers. Warfarin was administered in an individualized dose to achieve a stable reduction in prothrombin times calculated as International Normalized Ratio (INR) values. Then INR- and a drug concentration-time profile was determined. For the interaction phase, meloxicam was added for 7 days and then INR measurements and the warfarin drug profiles were repeated for comparison. Overall, warfarin treatment lasted for 30 days.


RESULTS
Warfarin and meloxicam were well tolerated by healthy volunteers in this study. Thirteen healthy volunteers with stable INR values entered the interaction phase. Prothrombin times, expressed as mean INR values, were not significantly altered by concomitant meloxicam treatment, being 1.20 for warfarin alone and 1.27 for warfarin with meloxicam cotreatment. R- and S-warfarin pharmacokinetics were similar for both treatments. Geometric mean (% gCV) AUCss values for the more potent S-enantiomer were 5.07 mg.h.l-1 (27.5%) for warfarin alone and 5.64 mg.h.l-1 (28.1%) during the interaction phase. Respective AUCss values for R-warfarin were 7.31 mg.h.l-1 (43.8%) and 7.58 mg.h.l-1 (39.1%).


CONCLUSIONS
The concomitant administration of the new non-steroidal anti-inflammatory drug (NSAID) meloxicam affected neither the pharmacodynamics nor the pharmacokinetics of a titrated warfarin dose. A combination of both drugs should nevertheless be avoided and, if necessary, INR monitoring is considered mandatory.
Türck
D
D
Department of Pharmacokinetics and Drug Metabolism, Biberach an der Riss, Germany.
Su
C A
CA
Heinzel
G
G
Busch
U
U
Bluhmki
E
E
Hoffmann
J
J
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D008297:Male; D000077239:Meloxicam; D011485:Protein Binding / Q000187:drug effects; D013237:Stereoisomerism; D013843:Thiazines / Q000008:administration & dosage / Q000494:pharmacology*; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D013843:Thiazines; D013844:Thiazoles; D014859:Warfarin; D000077239:Meloxicam