Koleva M, Dimova S
Laboratory of Drug Toxicology, Institute of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Methods Find Exp Clin Pharmacol. 2001 Dec;23(10):537-40. doi: 10.1358/mf.2001.23.10.677119.
The influence of long-term nifedipine administration on the antinociceptive activity of acetaminophen on hexobarbital sleeping time and liver monooxygenase and synthetase activities was studied in male albino mice. Nifedipine was administered orally at a dose of 25 mg/kg daily for 14 and 21 days. The nociceptive response was determined by the acetic acid writhing test. There was no significant difference in the antinociceptive effect of acetaminophen after treatment with nifedipine for 14 days. Nifedipine caused enzyme induction, which was demonstrated by shortened hexobarbital sleeping time, enhanced ethylmorphine-N-demethylase (EMND), aniline-4-hydroxylase (AH), ethoxycoumarine-O-deethylase (ECOD), UDP-glucuronyl transferase (UDPGT), glutathione-S-transferase (GST) and NADPH-cytochrome c reductase activity and increased content of cytochrome P450 and cytochrome b5. It is assumed that this effect of nifedipine on acetaminophen analgesia is associated with the changes (acceleration) in acetaminophen metabolism in the liver after repeated administration of the drug.
在雄性白化病小鼠中研究了长期给予硝苯地平对乙酰氨基酚的抗伤害感受活性、对戊巴比妥睡眠时间以及肝脏单加氧酶和合成酶活性的影响。硝苯地平以每日25mg/kg的剂量口服给药，持续14天和21天。通过醋酸扭体试验测定伤害感受反应。硝苯地平治疗14天后，乙酰氨基酚的抗伤害感受作用无显著差异。硝苯地平引起酶诱导，表现为戊巴比妥睡眠时间缩短、乙基吗啡-N-脱甲基酶（EMND）、苯胺-4-羟化酶（AH）、乙氧香豆素-O-脱乙基酶（ECOD）、尿苷二磷酸葡萄糖醛酸基转移酶（UDPGT）、谷胱甘肽-S-转移酶（GST）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。据推测，硝苯地平对乙酰氨基酚镇痛作用的这种影响与重复给药后肝脏中乙酰氨基酚代谢的变化（加速）有关。
