Dimova S, Koleva M, Rangelova D, Stoytchev T
Department of Drug Toxicology, Bulgarian Academy of Sciences, Sofia.
Pharmacol Toxicol. 1994 Nov;75(5):315-8. doi: 10.1111/j.1600-0773.1994.tb00366.x.
The effect of multiple nifedipine administration on hexobarbital sleeping time, liver monooxygenase and synthetase activities, lipid peroxidation and microsomal membrane fluidity were studied in male albino mice. The drug was administered orally at a dose of 25 mg/kg daily for 14 and 21 days. Nifedipine caused enzyme induction, demonstrated by shortened hexobarbital sleeping time, enhanced ethylmorphine N-demethylase, aniline 4-hydroxylase, ethoxycoumarine O-deethylase, UDP-glucuronyl transferase, glutathione S-transferase and NADPH-cytochrome c reductase activities and increased content of cytochrome P450 and cytochrome b5. This effect persisted until the 7th day after the last dose of nifedipine. There were no changes in lipid peroxidation and fluidity of the microsomal membranes after 14-day nifedipine administration. The increased cytochrome P450 content and drug metabolizing enzyme activities could be not associated with changes in these liver microsomal membrane properties.
在雄性白化病小鼠中研究了多次给予硝苯地平对己巴比妥睡眠时间、肝脏单加氧酶和合成酶活性、脂质过氧化和微粒体膜流动性的影响。药物以25mg/kg的剂量每日口服给药，持续14天和21天。硝苯地平引起酶诱导，表现为己巴比妥睡眠时间缩短、乙基吗啡N-脱甲基酶、苯胺4-羟化酶、乙氧基香豆素O-脱乙基酶、UDP-葡糖醛酸基转移酶、谷胱甘肽S-转移酶和NADPH-细胞色素c还原酶活性增强，以及细胞色素P450和细胞色素b5含量增加。这种效应一直持续到最后一剂硝苯地平给药后的第7天。给予硝苯地平14天后，脂质过氧化和微粒体膜的流动性没有变化。细胞色素P450含量增加和药物代谢酶活性增强可能与这些肝微粒体膜特性的变化无关。
