Yamaguchi Y
Nihon Eiseigaku Zasshi. 1989 Feb;43(6):1159-68. doi: 10.1265/jjh.43.1159.
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.
为了对已知会产生迟发性神经毒性（DNT）的有机磷杀虫剂溴苯磷进行药代动力学研究，利用高效液相色谱法开发了一种分析组织样品中溴苯磷的实用方法。采用该方法，研究了静脉注射溴苯磷后母鸡体内的药代动力学。获得了以下结果：1. 所提出的方法适用于生物组织中溴苯磷的分析。检测限为0.5纳克，回收率超过90%。2. 给药后母鸡体内溴苯磷的消失率在6小时时为70%，在96小时时为93%。通过双指数计算得出的半衰期，早期阶段为1.37小时，晚期阶段为45.53小时。由于在排泄物中检测到的溴苯磷仅为给药剂量的0.1%，其从母鸡体内消失是由于在母鸡组织中的代谢。3. 通过双指数计算得出的血液中溴苯磷的半衰期为0.50小时和7.57小时。4. 溴苯磷在组织中的下降模式彼此有很大差异。脂肪组织和坐骨神经中的溴苯磷浓度呈单指数下降，而其他组织（肝脏、肾脏、心肌、腿部肌肉、大脑和脊髓）中的溴苯磷呈双指数下降。溴苯磷从血液到组织的分布似乎非常迅速；然而，从组织到血液的再分布极其有限。5. 考虑到迟发性神经毒性的表现，溴苯磷在坐骨神经中的长半衰期尤其值得注意。6. 溴苯磷在肝脏中的短半衰期表明肝脏在溴苯磷代谢中起主要作用。7. 本研究结果与以下假设不一致，即像母鸡这样对迟发性神经毒性敏感的物种中溴苯磷的代谢比大鼠和小鼠等不敏感物种慢。也就是说，尽管本研究是在通常会出现神经损伤的实验条件下进行的，但溴苯磷代谢迅速。
