肠道CYP3A和P-gp:口服药物的吸收屏障  

The intestinal cytochrome P450 3A and P-glycoprotein:barriers to drug absorption

作　　者：王堃[1] 仲来福[1] 

机构地区：[1]大连医科大学药理学教研室，大连116027

出　　处：《中国药理学通报》2003年第9期988-991,共4页Chinese Pharmacological Bulletin

摘　　要：细胞色素P4 5 0 3A (CYP3A)亚族是人类药物代谢最重要的I相酶。由Mdr1基因编码的外向转运载体蛋白P糖蛋白 (P gp)为药物外排泵。这两种蛋白质在口服药物吸收的主要部位胃肠道均有高表达 ,同时二者的底物具有显著的重叠性。近来 ,大量研究表明 ,决定口服药物生物利用度的主要因素是肠道细胞CYP3A对已吸收药物的生物转化作用和肠道细胞中P gp对已吸收药物的主动外排作用。如果药物为CYP3A和 (或 )P gp的底物 ,当其与CYP3A和P gp的抑制剂同时服用后 。Cytochrome P450 3A (CYP3A/CYP3A4), the major phase I drug metabolizing enzyme in humans, and the Mdr1 gene expressed P glycoprotein (P gp), the drug efflux pump, are present at high levels in the villus tip of enterocytes of gastrointestinal tract, the primary site of absorption for orally administrated drugs, and share a significant overlap in substrate specificity. It has been recognized that metabolism by intestinal CYP3A/CYP3A4 is one of the major determinants of oral drug bioavailability. More recently, a large quantity of research has demonstrated that drug extrusion by intestinal P gp can both reduce drug absorption and modulate the effects of inhibitors and inducers of CYP3A/CYP3A4 mediated metabolism. A growing number of animal data and clinical studies, both in vitro and in vivo, have indicated that concomitant administration of CYP3A/CYP3A4 inhibitors and/or P gp inhibitors can increase the oral bioavailability of a wide range of drugs, which are CYP3A/CYP3A4 and P glycoprotein substrates.

关 键 词：细胞色素P450 CYP CYP3A CYP3A4 P糖蛋白 P-GP 口服生物利用度 肠道 

分 类 号：R341.32[医药卫生—基础医学] R345.99