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.
Han
K S
KS
College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul, South Korea.
Lee
M G
MG
D000818:Animals; D019540:Area Under Curve; D001711:Biotransformation; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics*
C104935:2-(allylthio)pyrazine; D001993:Bronchodilator Agents; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004791:Enzyme Inhibitors; D011719:Pyrazines; D013806:Theophylline