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© 1990 Oxford University Press

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Paraquat Pharmacokinetics Using a Subcutaneous Toxic Low Dose in the Rat

MICHAEL S. DEY*,1, ROGER G. BREEZE*,2, WILLIAM L. HAYTON{dagger}, ADEL H. KARARA{dagger},3 and ROBERT I. KRIEGER*,4

*WOI Regional Program in Veterinary Medical Education, University of Idaho Moscow 83843 {dagger}College of Pharmacy, Washington Stale University Pullman 99164

Received May 22, 1989; accepted June 6, 1989

Paraquat Pharmacokinetics Using a Subcutaneous Toxic Low Dose in the Rat. M. S. DEY, R. G. BREEZE, W. L. HAYTON, A. H. KARARA, AND R. I. KRIEGER. 1990. Fundam. Appl. Toxicol. 14, 208–216. The pharmacokinetics of paraquat were examined at a dose which produced lung disease but avoided renal damage. Following single sc injections of l4CH3-paraquat (72 µmol/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.


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