Inhibitory effect of 4-methylpyrazole on antipyrine clearance in rats.
Inhibitory effect of 4-methylpyrazole on antipyrine clearance in rats.
复制标题
4-甲基吡唑对大鼠安替比林清除的抑制作用。
DOI：
10.1016/0024-3205(92)90253-l
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发表时间：
1992
期刊：
影响因子：
6.1
通讯作者：
Mayersohn,M
中科院分区：
文献类型：
--
作者：
Chow,HH;Hutchaleelaha,A;Mayersohn,M
吡唑和4-甲基吡唑（4-MP）是有效的乙醇脱氢酶抑制剂。吡唑及其衍生物也已显示影响细胞色素P-450依赖性单加氧酶系统。研究了4-MP对安替比林（AP）分解动力学的影响。向雄性Fisher 344大鼠组ip注射4-MP（100 mg/kg）或4-MP HCl（相当于4-MP 100 mg/kg）或等体积的生理盐水。30分钟后经颈静脉导管静脉注射AP（20 mg/kg）。采集血液样品直至24小时，并通过HPLC进行分析。4-MP预处理显著降低AP清除率，从0.490 ± 0.032降至0.095 ± 0.014（4-MP HCl）和0.076 ± 0.008（4-MP）L/hr kg（p<0.01）。AP的分布容积从0.82 ± 0.07降至0.65 ± 0.06（4-MP HCl）和0.56 ± 0.04（4-MP）L/kg（p<0.05）。从1.68 ± 0.09增加到6.91 ± 0.58（4-MP HCl）和7.39 ± 0.56（4-MP）hr（p<0.01）。这些结果表明，4-MP对负责完整动物AP代谢的细胞色素P-450同工酶具有显著抑制作用。
Pyrazole and 4-methylpyrazole (4-MP) are potent, effective inhibitors of alcohol dehydrogenase. Pyrazole and its derivatives also have been shown to affect the cytochrome P-450 dependent monooxygenase system. This study was performed to investigate the effect of 4-MP on the disposition kinetics of antipyrine (AP). Groups of male Fisher 344 rats were given an ip injection of 4-MP (100 mg/kg) or 4-MP HCl (equivalent to 4-MP 100 mg/kg) or an equivalent volume of saline. AP (20 mg/kg) was injected intravenously via the jugular vein catheter 30 minutes later. Blood samples were collected upto 24 hours and assayed by HPLC. 4-MP pretreatment significantly decreased AP clearance from 0.490 ± 0.032 to 0.095 ± 0.014 (4-MP HCl) and 0.076 ± 0.008 (4-MP) L/hr kg (p<0.01). The volume of distribution of AP decreased from 0.82 ± 0.07 to 0.65 ± 0.06 (4-MP HCl) and 0.56 ± 0.04 (4-MP) L/kg (p<0.05). increased from 1.68 ± 0.09 to 6.91 ± 0.58 (4-MP HCl) and 7.39 ± 0.56 (4-MP) hr (p<0.01). These results demonstrate a significant inhibitory effect of 4-MP on the cytochrome P-450 isozyme(s) which is responsible for AP metabolism in intact animals.