Paraquat pharmacokinetics using a subcutaneous toxic low dose in the rat

Abstract

The pharmacokinetics of paraquat were examined at a dose which produced lung disease but avoided renal damage. Following single sc injections of 14CH 3 -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.