Effects of Meloxicam and Indomethacin on Cyclooxygenase Pathways in Healthy Volunteers

Abstract

Background

Meloxicam is a new NSAID with selectivity for the inducible cyclooxygenase (COX-2) in vitro. We compared the effects of therapeutically equivalent doses of meloxicam and indomethacin, a preferential inhibitor of the constitutive cyclooxygenase (COX-1), on platelet aggregation and platelet thromboxane formation, which are exclusively COX-1 dependent, physiological renal, and total body prostaglandin E₂ (PGE₂) production.

Methods

In a randomized cross-over design, 14 healthy female volunteers received meloxicam 7.5 mg per day for 6 days or indomethacin 25 mg three times per day for 3 days; the wash-out period was 5 days, and drug intake was adapted to the menstrual cycle. On the day before treatment and on the last day of each treatment period the following parameters were evaluated: maximum platelet aggregation and thromboxane B₂ (TXB₂) formation in response to 1.0 mmol/L arachidonic acid; 24-hour urinary excretion of PGE₂ and 7α-hydroxy-5,11-diketo-tetranor-prosta-1,16-dioic acid (PGE-M), the index metabolites of renal and total body PGE₂ synthesis, respectively, were assessed by gas chromatography/tandem mass spectrometry.

Results

Maximum platelet aggregation and TXB₂ formation were almost completely inhibited by indomethacin (-87% and-99%, respectively; p < 0.001, each) as compared to control (100%) but remained unaffected by meloxicam (-1% and +4%, respectively). Meloxicam showed no significant effects on urinary PGE₂ excretion (-13%) and only slight effects on PGE-M excretion (-22%; p < 0.05), whereas indomethacin reduced urinary PGE₂ excretion (-43%; p < 0.05) as well as PGE-M excretion (-36%; p < 0.001).

Conclusions

Our data show, that meloxicam 7.5 mg per day is COX-1 sparing in humans in vivo.