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.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)