Ishizuka Y, Sato M, Tanizawa H
Nihon Yakurigaku Zasshi. 1979 Sep;75(6):633-43.
The effect of M7310U, a new non-steroidal analgesic anti-inflammatory agent, on liver microsomal drug-metabolizing enzymes was investigated. Rats were treated orally with M73101 (100, 200, 500 mg/kg), henylbutazone (PZ, 200 mg/kg), aminopyrine (AM, 100 mg/kg) or phenobarbital sodium (PB, 100 mg/kg) once daily for 2 weeks and then were observed for 2 weeks during which treatment was not given. On treatment with M73101, PZ, AM and PB, the liver enlarged but was restored to normal 1 week after the last administration. The rate of increase in the case of M73101 was lower than that seen with the reference compounds. M73101 markedly increased the content of microsomal protein, cytochrome P-450 or b5 and NADPH cytochrome C reductase, aniline hydroxylase and AM demethylase activity, but these increments returned to the normal level 1 week after the last administration. The serum concentration of M73101 after repeated administration (200 mg/kg, p.o.) for 1 week was lower than that after a single administration. Furthermore, M73101 increased Vmax for both aniline hydroxylase and AM demethylase, whereas it increased Km only for aniline hydroxylase. M73101 did not enhance the lipid peroxidation. Our observations suggest that the enlargement of rat liver seen with M73101 was due to the induction of drug-metabolizing enzymes and that this agent can probably be classified as a phenobarbital-type inducer.
研究了新型非甾体镇痛抗炎药M7310U对肝微粒体药物代谢酶的影响。大鼠每天口服一次M73101（100、200、500mg/kg）、苯基丁氮酮（PZ，200mg/kg）、氨基比林（AM，100mg/kg）或苯巴比妥钠（PB，100mg/kg），持续2周，然后停药观察2周。用M73101、PZ、AM和PB治疗后，肝脏肿大，但在末次给药后1周恢复正常。M73101导致的肝脏肿大程度低于参比化合物。M73101显著增加微粒体蛋白、细胞色素P-450或b5以及NADPH细胞色素C还原酶的含量、苯胺羟化酶和AM脱甲基酶活性，但这些增加在末次给药后1周恢复到正常水平。重复给药（200mg/kg，口服）1周后M73101的血清浓度低于单次给药后。此外，M73101增加了苯胺羟化酶和AM脱甲基酶的Vmax，而仅增加了苯胺羟化酶的Km。M73101未增强脂质过氧化作用。我们的观察结果表明，M73101导致大鼠肝脏肿大是由于药物代谢酶的诱导，并且该药物可能可归类为苯巴比妥型诱导剂。
