Paraquat pharmacokinetics using a subcutaneous toxic low dose in the rat.
The pharmacokinetics of paraquat were examined at a dose which produced lung disease but avoided renal damage. Following single sc injections of 14CH3-paraquat (72 mumols/kg) in male Sprague-Dawley rats, blood was sampled via indwelling jugular cannulas. Noncannulated rats were exsanguinated by cardiac puncture during a 7-day test period. Blood, liver, kidney, lung, brain, heart, spleen, gi tract, injection site, adrenals, body, urine, and feces were analyzed for total radioactivity. Histology of lung after 7 days revealed (+1) paraquat lung disease. No evidence of renal damage was observed. Paraquat was rapidly absorbed. Peak blood concentrations of 58 nmol/ml were measured at 20 min. Peak lung and kidney paraquat concentrations at 40 min were 65 and 359 nmol/g, respectively. Paraquat pharmacokinetics (NONLIN) were best described by a two-compartment open model; the mean biological half-life was 40.9 hr. Eighty-five percent of the dose was eliminated in urine by 7 days. The body contained 79% of the remaining radioactivity. The residual radioactivity is associated with prolonged paraquat excretion and, perhaps, progressive lung disease.
Dey
M S
MS
WOI Regional Program in Veterinary Medical Education, University of Idaho, Moscow 83843.
Breeze
R G
RG
Hayton
W L
WL
Karara
A H
AH
Krieger
R I
RI
D000818:Animals; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D010269:Paraquat / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D010269:Paraquat