[The biotransformation of NSAIDs: a common elimination site and drug interactions].
Many NSAIDs are eliminated predominantly through hepatic biotransformation in man. We have studied, in human hepatic microsomes, the role of specific cytochrome P450 isozymes in the formation of the major metabolites of oxicam (piroxicam and tenoxicam), phenylacetic (diclofenac) and propionic acid (ibuprofen) derivatives. A common isozyme (P450TB, CYP2C subfamily) controls the major elimination pathway of these NSAIDs. We have also determined, in two in vitro models of P450TB, the affinity for this isozyme of NSAIDs from other chemical classes (acetylsalicylic acid, mefenamic acid and indomethacin). All NSAIDs tested displayed a high affinity (3-300 microM) for cytochrome P450TB. Cytochrome P450TB plays a major role in the elimination of several NSAIDs with different chemical structures. NSAIDs are substrates as well as potential inhibitors of cytochrome P450TB. Their elimination can therefore be reduced by concomitant administration of known inhibitors of P450TB (antifungals, antibacterial sulfonamides, calcium channel blockers).
Leemann
T
T
Division de Pharmacologie clinique et Consultation commune de la douleur, Hôpital cantonal universitaire, Genève.
Kondo
M
M
Zhao
J
J
Transon
C
C
Bonnabry
P
P
Dayer
P
P
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System
La biotransformation des AINS: un site commun d'élimination et d'interactions médicamenteuses.