title: The mechanism of excretion of paraquat in rats.
abstract: Paraquat (PQ)(1,1'-dimethyl-4,4'-bipyridinium) is a toxic herbicidal cation. The renal excretory mechanisms of PQ and its interactions with organic cations and anions were investigated in anaesthetised rats. The renal clearance of PQ was studied in male Wistar rats using inulin as the marker of glomerular filtration rate. The fractional excretion of paraquat (FEpq) decreased from 2.1+/-0.01 to 1.2+/-0.03 as the plasma concentration rose from 0.4+/-0.02 to 21.2+/-1.6 microM. These results demonstrated that the excretion of PQ was greater than glomerular filtration, concentration dependent and saturable, indicating that it was secreted by an active transport system. The excretion of PQ was dependent predominantly on the glomerular filtration rate with a small secretory component (Km = 8.5+/-3.1 microM, Vmax = 114+/-19 nmol/kg per min). The clearance of PQ was not inhibited by high doses of cimetidine, or p-aminohippurate. However, quinine (P = 0.001) and N-methylnicotinamide (NMN) (P = 0.03) reduced the FEpq, suggesting that they share a similar cation transport system with PQ. In summary, PQ is actively secreted by the rat kidney via a cation transport system.
authors.affiliation: Department of Renal Medicine and Toxicology Unit, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. bchan@renicu.rpa.cs.nsw.gov.au
authors.forename: B S
authors.initials: BS
authors.lastname: Chan
authors.forename: J P
authors.initials: JP
authors.lastname: Seale
authors.forename: G G
authors.initials: GG
authors.lastname: Duggin
mesh_terms: D000818:Animals; D000838:Anions / Q000494:pharmacology; D001667:Binding, Competitive / Q000502:physiology; D002412:Cations / Q000494:pharmacology; D008297:Male; D010269:Paraquat / Q000493:pharmacokinetics* / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000838:Anions; D002412:Cations; D010269:Paraquat