INFLUENCE OF CIGARETTE-SMOKE ON ANTIPYRINE METABOLITE FORMATION IN RATS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 41  (3) , 473-491
Abstract
The effect of cigarette smoke in rats on antipyrine (AP) disposition in blood and AP metabolites in urine were studied and compared to results obtained after pretreatment with tar, 3-methylcholanthrene (3-MC) and phenobarbital (PB). In vitro hepatic monooxygenase activities were also examined in smoke-exposed and tar-pretreated rats and compared to saline-pretreated or controls. The smoke-exposed and tar-pretreated rats showed a significant (P < 0.05) increase in AP clearance as comapred to controls. The increases in AP clearance of PB and 3-MC groups were more remarkable (P < 0.01), being > 3- and 8-fold greater than the control group, respectively. The urinary amount of 4-hydroxyantipyrine (40HA) was significantly (P < 0.05) greater and that of norantipyrine (NORA) and AP less (P < 0.05) in the smoke-exposed rats than in the controls. This trend was not observed in the tar-pretreated rats. In the 3-MC-treated rats a significant (P < 0.05) increase in the urinary amount of 40HA was found, while that of 3HMA was significantly (P < 0.01) diminished without a change in AP or NORA in the urine. In the PB-pretreated rats the trend was similar to the 3-MC group except that the amount of unchanged AP was significantly (P < 0.05) decreased. In the study of in vitro hepatic monooxygenase activities 7-ethoxycoumarin O-deethylase was significantly (P < 0.01) increased in the smoke-exposed rats but not in the tar-treated rats. There was no significant increase in the content of cytochrome P-450 or aminopyrine N-demethylase in the 2 groups. The metabolic pathways of AP, a multimetabolized drug, probably was affected differently with different experimental inducers and smoke and tar acted differently on the hepatic monooxygenase system resulting in the different profiles of AP metabolites in rate urine.