MDR和cyp3a4介导的药物-药物相互作用。

文章的细节

引用

复制到剪贴板

Pal D, Mitra AK

MDR和cyp3a4介导的药物-药物相互作用。

中华神经免疫杂志，2006;1(3):323-39。Epub 2006 8月2日

PubMed ID

18040809 (PubMed视图

]

摘要

p -糖蛋白(P-gp)、多重耐药相关蛋白(MRPs)和细胞色素P450 3A4共同构成了许多口服吸收药物的高效屏障。已知多药方案和相应的药物-药物相互作用会导致许多药物不良反应和治疗失败。现有文献、临床报告和我们实验室的体外研究表明，许多药物都是P-gp和CYP3A4的底物。我们的主要假设是，当与唑类抗真菌药物、大环内酯类药物、氟喹诺酮类抗生素、他汀类药物、心血管药物、免疫调节剂和娱乐性药物[苯二氮平类药物、可卡因、麦角酸二乙基酰胺(LSD)、大麻、安非他明(甲基安非他明)、3,4-亚甲基二氧甲基苯丙胺(MDMA)和阿片类药物]联合使用时，蛋白酶抑制剂(pi)和nnrti的转运和代谢会因外排和/或细胞靶代谢而改变。因此，这种药物组合可能是导致意外和无法解释的治疗结果的原因。本文讨论了一些关于pi与其他类药物(大环内酯类抗生素、唑类抗真菌药物、降胆固醇他汀类药物、心血管药物和免疫调节剂)相互作用的临床报告。采用MDCKII-MDR1作为体外模型，评价抗逆转录病毒药物、唑类抗真菌药物、大环内酯类和氟喹诺酮类抗生素对外排转运体的影响。酮康唑(50mum)可提高细胞内(3)H利托那韦的浓度。酮康唑与MK 571对(3)H利托那韦外排的抑制作用具有可比性。酮康唑与MK 571同时掺入有加性效应。 Results of (3)H ritonavir uptake studies were confirmed with transcellular transport studies. Several fluroquinolones were also evaluated on P-gp-mediated efflux of (3)H cyclosporin and 14C erythromycin. These in vitro studies indicate that grepafloxacin, levofloxacin, and sparfloxacin are potent inhibitors of P-gp-mediated efflux of 14C erythromycin and (3)H cyclosporin. Simultaneous administration of fluoroquinolones and macrolides could minimize the efflux and metabolism of both of the drugs. Effects of erythromycin and ketoconazole on carbamazepine metabolism were examined. Formation of 10,11-epoxy carbamazepine, a major CBZ metabolite, was significantly inhibited by these agents. Therefore, drug efflux proteins (P-gp, MRPs) and metabolizing enzyme (CYP450) are major factors in drug interactions. Overlapping substrate specificities of these proteins result in complex and sometimes perplexing pharmacokinetic profiles of multidrug regimens. Drug-drug interactions with PIs and other coadministered agents for human immunodeficiency virus (HIV) positive population have been discussed in light of efflux transporters and metabolizing enzymes. This article provides an insight into low and variable oral bioavailability and related complications leading to loss of therapeutic activity of MDR and CYP 450 substrates.

引用本文的药物库数据

药物酶

药物	酶	种类	生物	药理作用	行动
Grepafloxacin	细胞色素P450 3A4	蛋白质	人类	未知的	底物	细节