Effects of ethanol on pharmacokinetics and intestinal absorption of paraquat in animals.
The effect of ethanol on pharmacokinetics of paraquat was studied in rabbits by intravenous (i.v.) bolus injection of ethanol 0.5 g/kg (or normal saline, in the control group) followed by an i.v. dose of paraquat 20 mg/kg. A greater apparent volume of distribution (Vd), faster distribution rate constants and lower peak plasma concentration (P < 0.01) of paraquat were observed in the ethanol-treated than that in the control rabbits. The total clearance of paraquat was not significantly different between the two groups. The effect of ethanol on the intestinal absorption of paraquat was estimated by in situ intestinal perfusion technique in rats. The perfusate contained paraquat 50 micrograms/ml alone or with 1% or 2% ethanol. Inulin 320 micrograms/ml was added to the perfusate for the measurement of water net flux. The absorption clearance of paraquat as well as the absorption of water increased (P < 0.01) about two-fold in the presence of ethanol. The results of this study suggest that ethanol may potentiate paraquat toxicity by increasing intestinal absorption and tissue distribution. The critical lethal plasma concentration of paraquat is supposed to be lower in the presence of ethanol owing to increased volume of distribution.
Yu
H Y
HY
School of Pharmacy, Department of Legal Medicine, College of Medicine, National Taiwan University, Taipei, R.O.C.
Lai
Y R
YR
Kuo
T L
TL
Shen
Y Z
YZ
D000818:Animals; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D010269:Paraquat / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010477:Perfusion; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D014018:Tissue Distribution / Q000187:drug effects
D000431:Ethanol; D010269:Paraquat