摘要
为探讨质子泵抑制剂 (PPI)盘托拉唑 (PAN)对大鼠肝药酶中药物代谢酶的影响 ,给试验大鼠连续7天口服不同剂量〔5 m g/ (kg· d)、5 0 m g/ (kg· d)和 30 0 mg/ (kg· d)〕的 PAN,而后测定大鼠肝药酶中细胞色素P45 0 (P45 0 )、细胞色素 b5 (b5 )、NADPH细胞色素 C还原酶 (NADPH)的含量和活性变化 ,以及细胞色素 P45 0同功酶 (CYP)的活性变化 ,并与奥美拉唑 (OM)、兰索拉唑 (L AN)、3-甲基胆醌 (3- MC)和苯巴比妥 (PB)比较。结果 :口服高剂量〔30 0 m g/ (kg· d)〕PAN后大鼠肝药酶中 P45 0、b5 以及 NADPH的含量和活性升高 ,但不及 PB的作用强 ,其中 3- MC对 NADPH的作用最弱 ,CYP1A、CYP2 B和 CYP3A的活性也升高 ,且 3- MC对 CYP1A作用极强 ,PB对 CYP2 B和 CYP3A的作用最强。三个 PPI中 ,OM和 L AN在同一条件下比 PAN更易引起 CYP1A活性的升高 ,PAN对 CYP2 B的作用强于 OM和 L AN。上述结果表明 ,PAN与 OM和 L AN对肝药酶中代谢酶的作用类似 ,但作用更弱 ,并提示 PAN在体内代谢中具有更小的药物相互作用性。
This study was aimed to assess investigate the effect of proton pump inhibitor pantoprazole(PAN) on metabolic enzymes in rat liver microsomes. Different doses of pantoprazole, 5 mg/(kg·d), 50 mg/(kg·d), and 300mg/(kg·d) for 7 days were administrated respectively. The changes of cytochrome P450, cytochrome b 5, NADPH cytochrome c reducase and P450 isozymes levels after the administration of PAN were assayed and compared with those after the use of 3 mehtylcholanthrene(3 MC), phenobarbital(PB), omeprazole(OM) and lansoprazole (LAN). The results should that high dose PAN increased the levels of cytochrome P450, cytochrome b 5 and NADPH cytochrome c reducase, but PAN was less effectual as compared with PB. The levels of CYP1A, CYP2B and CYP3A went up after the administration of PAN for 7 days. In comparison, OM and LAN were stronger in increasing the level of CYP1A, and they showed stronger interaction in drug metabolism. In contrast, PAN had slight effect on CYP 1A and weak interaction with other drugs in metabolism. These data suggested that PAN might be a weak interaction drug in metabolizing.
出处
《华西医科大学学报》
CAS
CSCD
2000年第4期449-451,共3页
Journal of West China University of Medical Sciences
