Alteration of drug kinetics in rats following exposure to trichloroethylene.
The effect of trichloroethylene (TCY) was investigated to determine whether repeated exposure alters the pharmacokinetics of some drugs. Sprague-Dawley rats were given intraperitoneal injections of TCY (5 mmol/kg) in corn oil once daily for 3 days, while the control group received only corn oil. Four hours after the last dose, theophylline, quinidine, or pentobarbital were administered. Blood samples were collected at appropriate intervals for drug analyses. There was a small decrease in plasma clearance of theophylline, with no change in volume of distribution (V(d)) as compared with controls. For quinidine, the elimination half-life was unchanged, and the V(d) was decreased by 40%. The clearance of pentobarbital was decreased by 40% in male rats, but not in the females. Nonetheless, the duration of the sleeping time for both sexes was remarkably prolonged as compared with the control group. There was a decrease in the cytochrome P-450 content only in male rats. In conclusion, exposure to TCY causes changes in some drug kinetics, probably resulting from differential effects on the drug-metabolizing enzymes.
Kukongviriyapan
V
V
Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Simajareuk
S
S
Kukongviriyapan
U
U
Cha-on
U
U
Airarat
W
W
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics; D005260:Female; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics; D008297:Male; D010424:Pentobarbital / Q000493:pharmacokinetics; D010599:Pharmacokinetics; D010726:Phosphodiesterase Inhibitors / Q000493:pharmacokinetics; D011802:Quinidine / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D012997:Solvents / Q000493:pharmacokinetics*; D013806:Theophylline / Q000493:pharmacokinetics; D014241:Trichloroethylene / Q000493:pharmacokinetics*
D004791:Enzyme Inhibitors; D006993:Hypnotics and Sedatives; D010726:Phosphodiesterase Inhibitors; D012997:Solvents; D014241:Trichloroethylene; D003577:Cytochrome P-450 Enzyme System; D013806:Theophylline; D010424:Pentobarbital; D011802:Quinidine