磺胺多辛在鲆鲽鱼体内代谢动力学的分析研究及生理药动学模型初探.pdfVIP

肤中的残留浓度很高，皮肤应作为残留监控的靶组织；依据消除规律和最大残留 限量（MRL ）的规定，在本实验条件下，建议休药期不低于37 d，777 度日。 本研究假设磺胺多辛以原药形式存在，根据磺胺多辛在牙鲆体内的分布、转 运、代谢特点，设计了包含血液、肌肉、肝脏、肾脏、皮肤和其他等 6 大模块的 模型结构，建立了磺胺多辛在牙鲆体内的生理药动学模型，描述了磺胺多辛在牙 鲆体内的残留消除情况，并采用最大似然法计算并校正模型参数，进行了模型参 数的灵敏性分析，比较了预测值与实测值的相关性和吻合程度，结果表明，组织 -血浆分配系数、肾清除率、器官容积比是对模型影响最大的灵敏性参数，生药 模型拟合的浓度值与实测浓度值吻合较好，能够准确反映磺胺多辛在牙鲆体内的 残留消除情况。将模型外推至半滑舌鳎，模型准确地预测了半滑舌鳎的残留消除 规律，说明了所建立的磺胺多辛在牙鲆体内的生药模型的具有可靠的药物残留预 测能力。 综上所述，磺胺多辛在鲆鲽鱼体内的代谢动力学研究和生药模型的建立，为 丰富我国水产动物的基础药动学数据做出贡献，为开展水产品药物残留预测评估 提供科学依据。 关键词：磺胺多辛 牙鲆 半滑舌鳎 代谢动力学 生理药动学模型 II 万方数据 Study of Pharmacokinetics and Establishment of Physiological Pharmacokinetic Model (PBPK) of Sulfadoxine in Flounders Abstract Sulfadoxine (SDM′) is a chemical synthetic and broad-spectrum antimicrobials, which have a very good antibacterial effect on aquaculture fish. Therefore, SDM′ is slowly excreted from the fish. The residues of SDM′ will be harm to consumers seriously through of the food chain. SDM′ has been listed as drug residue monitoring object at home and abroad. There are little studies of pharmacokinetics and no establishment of physiological pharmacokinetic model of Sulfadoxine in flounders. This paper systematically studied the pharmacokinetics and residues elimination, and exploringly established the physiological pharmacokinetic model of Sulfadoxine in Paralichthys olivaceus and Cynoglossus semilaevis, respectively. In the 22±2 ℃ seawater, the pharmacokinetics of SDM′ was studied in plasma and tissues of P. olivaceus after single 200 mg/kg·b