Effect of subacute methyl parathion administration on the pharmacokinetics and pharmacodynamics of nifedipine in rats

Families living in agricultural areas may submitted to repeated exposure of methyl parathion (MP) that has been widely used as an agricultural insecticide. MP inhibits cytochrome P450 enzymes and has the potential to alter pharmacokinetic profiles of therapeutic agents that are metabolized in the liver. The aim of the present study is to investigate the possibility that the increased pharmacokinetic and pharmacodynamic effects of nifedipine is due to the inhibition of the metabolism after repeated administration of low doses of MP in rats. Male rats received commercial formulation of diluted MP (1/100 LD50 or 1/25 LD50, n = 6) or tap water (control, n = 5) via gastric gavage (0.5 ml) for 14 days. On the 15th day, the carotid artery and jugular vein were cannulated for measurement of cardiovascular parameters and blood sampling, respectively. Nifedipine was administered 3 mg/ka via the cannula inserted in the duodenum of the rat. Subacute NIP administration did not change pharmacokinetic AUC((0-240)), C-max, t(max), t(1/2)) and pharmacodynamic (mean arterial pressures and heart rates) parameters of nifedipine. These findings provide evidence that repeated exposure of low doses of commercial MP did not affect the elimination of nifedipine which might be due to the lack of inhibition of CYP3A in rats. (C) 2006 Elsevier B.V. All rights reserved.