¹Department of Experimental and Clinical Pharmacology and Toxicology, University Erlangen/Nürnberg. Erlangen, Germany

Correspondence: Gerd Geisslinger PhD, MD, Center of Pharmacology, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. E-mail: geisslinger@em.uni-frankfurt.de

^*Supported by BMBF (Bundesministerium für Bildung und Forschung, Germany; 01 EC 9403) and in part by a grant from Ciba-Geigy, Wehr, Germany, and Asta Medica AWD, Frankfurt am Main, Germany.

Received 12 August 1998; Accepted 14 December 1998.

Abstract

Objective: To evaluate the extent of human cyclooxygenase-1 (COX-1) inhibition by meloxicam, which has been reported to preferentially inhibit cyclooxygenase-2 (COX-2). The effects of meloxicam were compared with those of diclofenac, a nonselective COX inhibitor.

Methods: COX-1 inhibition was determined by measuring thromboxane B₂ (TXB₂)–generation from clotting whole blood ex vivo after single oral doses of 7.5 and 15 mg meloxicam and 75 mg diclofenac and at steady state (15 mg meloxicam daily and 150 mg diclofenac daily). The effect was expressed as percentage inhibition of serum TXB₂ generation and was directly related to the serum drug concentration with use of a standard sigmoidal E_max model.

Results: In terms of inhibition of TXB₂ generation, diclofenac was about 1 order of magnitude more potent than meloxicam, indicated by a diclofenac EC₅₀ (concentration of drug required to cause 50% of maximum effect) that was about 10 times lower than that of meloxicam (EC₅₀ diclofenac single doses: 37.50 29.64; EC₅₀ meloxicam single doses: 677.50 189.08). However, serum concentrations of meloxicam after administration of 15 mg were approximately 10-fold higher than those of diclofenac. Therefore there was no statistically significant difference in the area under the effect time curve (P = .115) and the mean effect (P = .424) between meloxicam and diclofenac. The EC₅₀ of both drugs was significantly higher at steady state (diclofenac steady state: 87.07 55.24 ng/mL; meloxicam steady state: 1850.12 829.93 ng/mL) than after a single dose (P < .001).

Conclusion: These data show that meloxicam inhibits TXB₂ generation at clinically relevant doses, although less potently than diclofenac. Thus our data suggest that the COX-2 preference of meloxicam observed in vitro may not result in clinical advantages when the higher dose of 15 mg is needed. Because of the increase in EC₅₀ at steady state, COX-1 is relatively spared when the lower dose of 7.5 mg is administered.