Leemann T, Kondo M, Zhao J, Transon C, Bonnabry P, Dayer P
Division de Pharmacologie clinique et Consultation commune de la douleur, Hôpital cantonal universitaire, Genève.
Schweiz Med Wochenschr. 1992 Dec 5;122(49):1897-9.
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).
许多非甾体抗炎药在人体内主要通过肝脏生物转化而消除。我们在人肝微粒体中研究了特定细胞色素P450同工酶在形成恶丙嗪（吡罗昔康和替诺昔康）、苯乙酸（双氯芬酸）和丙酸（布洛芬）衍生物的主要代谢产物中的作用。一种常见的同工酶（P450TB，CYP2C亚家族）控制着这些非甾体抗炎药的主要消除途径。我们还在P450TB的两种体外模型中测定了其他化学类别的非甾体抗炎药（乙酰水杨酸、甲芬那酸和吲哚美辛）对该同工酶的亲和力。所有测试的非甾体抗炎药对细胞色素P450TB均表现出高亲和力（3 - 300微摩尔）。细胞色素P450TB在消除几种具有不同化学结构的非甾体抗炎药中起主要作用。非甾体抗炎药既是细胞色素P450TB的底物，也是其潜在抑制剂。因此，同时给予已知的P450TB抑制剂（抗真菌药、抗菌磺胺类药物、钙通道阻滞剂）可减少它们的消除。
