[Pharmacokinetics of the organophosphorous insecticide leptophos in the hen].

In an attempt to carry out a pharmacokinetic study of the organophosphorous insecticide leptophos, which is known to produce delayed neurotoxicity (DNT), a practical method for the analysis of leptophos in tissue samples has been developed by utilizing high-performance liquid chromatography. Using this method, the pharmacokinetics of intravenously administered leptophos in hens were investigated. The following results were obtained: 1. The proposed method was suitable for the analysis of leptophos in biological tissues. The detection limit was 0.5 ng and the recovery rate was over 90%. 2. The disappearance rate of leptophos in hens after administration was 70% at 6 hours and 93% at 96 hours. The half-lives calculated bi-exponentially were 1.37 hours for the early phase and 45.53 hours for the late phase. Since the leptophos detected in excreta was only 0.1% of the administered dose, its disappearance from the hen's body was due to its metabolization in the hen's tissue. 3. The half-lives of leptophos in blood calculated bi-exponentially were 0.50 and 7.57 hours. 4. The decline patterns of leptophos in tissue were considerably different from each other. While leptophos concentrations in adipose tissue and sciatic nerves decreased mono-exponentially, leptophos in other tissues (liver, kidney, heart muscle, leg muscle, brain and spinal cord) decreased bi-exponentially. The distribution of leptophos from blood to tissue seemed to be very rapid; however, redistribution from tissue to blood was extremely limited. 5. The long half-life of leptophos in sciatic nerves was especially noteworthy considering the manifestation of DNT. 6. The short half-life of leptophos in liver indicated the predominant role of liver in leptophos metabolism. 7. The results of this study do not coincide with the hypothesis that the metabolism of leptophos in species susceptible to DNT such as hens is slower than in non-susceptible species such as rats and mice. That is, in spite of the fact that this study was carried out under experimental conditions in which nerve damage would normally be manifested, leptophos was metabolized rapidly.