Comparison of inhibitory effects of meloxicam and diclofenac on human thromboxane biosynthesis after single doses and at steady state

Citation
I. Tegeder et al., Comparison of inhibitory effects of meloxicam and diclofenac on human thromboxane biosynthesis after single doses and at steady state, CLIN PHARM, 65(5), 1999, pp. 533-544
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOLOGY & THERAPEUTICS
ISSN journal
0009-9236 → ACNP
Volume
65
Issue
5
Year of publication
1999
Pages
533 - 544
Database
ISI
SICI code
0009-9236(199905)65:5<533:COIEOM>2.0.ZU;2-6
Abstract
Objective: To evaluate the extent of human cyclooxygenase-l (COX-1) inhibit ion by meloxicam, which has been reported to preferentially inhibit cycloox ygenase-2 (COX-2), The effects of meloxicam were compared with those of dic lofenac, a nonselective COX inhibitor. Methods: COX-1 inhibition was determined by measuring thromboxane B-2 (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 melo xicam daily and 150 mg diclofenac daily). The effect was expressed as perce ntage inhibition of serum TXB2 generation and was directly related to the s erum 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 EC 50 (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 appro ximately 10-fold higher than those of diclofenac, Therefore there was no st atistically 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 (diclofena c 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 clin ically relevant doses, although less potently than diclofenac. Thus our dat a 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. Beca use of the increase in EC50 at steady state, COX-1 is relatively spared whe n the lower dose of 7.5 mg is administered.