THE MECHANISM OF EXCRETION OF PARAQUAT IN RATS

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. T he 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 mu M. Thes e results demonstrated that the excretion of PQ was greater than glome rular filtration, concentration dependent and saturable, indicating th at it was secreted by an active transport system. The excretion of PQ was dependent predominantly on the glomerular filtration rate with a s mall secretory component (K-m = 8.5 +/- 3.1 mu M, V-max = 114 +/- 19 n mol/kg per min). The clearance of PQ was not inhibited by high doses o f 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 i s actively secreted by the rat kidney via a cation transport system. C opyright (C) 1997 Elsevier Science Ireland Ltd.