摘要
目的为了解有机磷类杀虫剂——甲胺磷在大鼠体内的吸收、分布、代谢、排泄和毒性。方法采用暴露相关的剂量估算模型(ERDEM)构建大鼠的生理药代动力学/药效学模型。模型结构包括完整的胃肠道、肝脏代谢、尿排泄、粪便消除以及甲胺磷对乙酰胆碱酯酶(ACh E)的双分子模式抑制。结果该模型可对多种给药途径后的血药浓度进行拟合。尿中累积排泄率为剂量的52.7%,粪消除为剂量的2.4%(相应的实验数据为52%和2.7%)。对大鼠血液及脑内ACh E活性亦有近似的模拟。对一组未用于模型优化的血ACh E活性剂量效应的模拟证明模型具有优良的预测能力。结论所构建的甲胺磷的大鼠PBPK/PD模型有助于甲胺磷的健康风险评估和多个有机磷的累积风险评估。
Objective To characterize the disposition and toxicity for an organophosphate pesticide—methamidophos in the rat. Methods ERDEM was used to build the rat PBPK / PD model. Model structures included a full gastrointestinal compartment,liver metabolism,urinary excretion,fecal elimination,and bimolecular ACh E inhibition. Results The model could closely simulate the blood concentration time history data by various exposure routes. The cumulative urinary excretion was 52. 7% and cumulative fecal elimination was 2. 4% by the model（ corresponding experimental measurement was 52% and 2. 7%,respectively）. Simulation to the ACh E activity in the blood and brain was also satisfactory. Model simulation to a dose response curve which was not used in the model calibration showed the model could replicate the relationship between dose and ACh E activity in the blood. Conclusion The constructed model will be useful in the risk assessment for methamidophos and the cumulative risk assessment for multiple organophosphate pesticides.
出处
《实用药物与临床》
CAS
2015年第2期174-177,共4页
Practical Pharmacy and Clinical Remedies
