Effect of a new chemoprotective agent, 2-(allylthio)pyrazine, on the pharmacokinetics of intravenous theophylline in rats.

The effect of 2-(allylthio)pyrazine (2-AP) pretreatment on the pharmacokinetics of theophylline and its metabolites was investigated after 1-min intravenous administration of aminophylline, 5 mg/kg as theophylline, to rats pretreated with three consecutive daily oral administration of 2-AP, 100 mg/kg. The AUC0-2 h of a metabolite of theophylline, 1,3-dimethyluric acid, 1,3-DMU (62.3 versus 106 microg/min per ml), and the percentages of intravenous dose of theophylline excreted in 24-h urine as 1,3-DMU (12.4% versus 20.8%, expressed in terms of theophylline) decreased significantly in 2-AP-pretreated rats when compared with those in control rats. Since CYP1A2 and CYP2E1 are involved in the formation of 1,3-DMU from theophylline, and 2-AP considerably suppressed CYP2E1 and tended to suppress CYP1A2 in rats, decreased formation of 1,3-DMU in 2-AP-pretreated rats could be mainly due to suppression of the CYP2E1 expression by pretreatment with 2-AP.