己烯雌酚及代谢物在草鱼(Ctenopharynodon idellus)体内的组织分布及药物代谢动力学研究

Tissue Distribution and Pharmacokinetics of Diethylstilbestrol and Its Metabolite Dienestrol in Ctenopharynodon idellus

研究了口服灌药给药方式下,己烯雌酚及其主要代谢物双烯雌酚在草鱼(Ctenopharynodon idellus)体内的组织分布和药物代谢动力学。血浆、肌肉和肝脏中浓度-时间曲线符合一级吸收二室开放动力学模型。以1.0 mg/kg b.w.为例,己烯雌酚峰值水平肝脏最高、肌肉次之、血浆最低,平均消除速率分别为12.02μg/(L·h)、1.33μg/(kg·h)和3.59μg/(kg·h),10 h、192 h和168 h均降至检出限以下。代谢物双烯雌酚变化趋势与己烯雌酚相似,在血浆、肌肉和肝脏中1 h、6 h和6 h达到最大浓度值,8 h、168 h和144 h降至检出限以下。采用DAS2.0计算有关药物代谢动力学参数。血浆、肌肉、肝脏的AUC相差较大,不同组织对己烯雌酚的蓄积能力有所差别;血浆、肌肉和肝脏的CL/F值较小,说明其在草鱼体内分布广,消除较快。建议其消除期分别定为6 d、8 d和10 d。本研究所得的药时曲线可为草鱼己烯雌酚的消除净化提供数据支持。

Diethylstilbestrol and its metabolite dienestrol in Ctenopharynodon idellus by oral administration were investigated in their tissue distribution and pharmacokinetics, and they were quantified by UPLC-MS. Diethylstilbestrol concentrations-versus-time was well described by a two-department open model with first-order absorption. For example, after single oral of 1.0 mg/kg （b.w.） diethylstilbestrol, the highest concentration of it was detected in liver, followed by muscle and plasma. The average elimination speed was 12.02 μg/（kg·h）, 1.33 μg/（kg·h） and 3.59 μg/（kg·h）, respectively, for plasma, muscle and liver. No diethylstilbestrol was detected after oral administration of 10 h, 192 h and 168 h. The variation of dienestrol concentrations in plasma, muscle and liver of Ctenopharynodon idellus was similar to that of diethylstilbestrol, which was increased first and then decreased. Concentrations of dienestrol in plasma, muscle and liver reached the peak after oral administration of 1 h, 6 h and 6 h, and no detection after 8 h, 168 h and 144 h. The relevant pharmacokinetic parameters of diethylstilbestrol were calculated by using DAS 2.0. Taking the concentration of 1.0 mg/kg b.w. diethylstilbestrol as example, it was indicated that area under concentration-time curve （AUC） differed greatly and the tissues had different accumulation capability. The overall clearance rate was 1.434 L/（h·kg）, 0.126 L/（h·kg） and 0.099 L/（h·kg）, indicating diethylstilbestrol was widely distributed and fast eliminated in tissue. It was recommended the eliminated period should be 6 d, 8 d and 10 d. The concentrations versus time curve of diethylstilbestrol provided useful information for studying decontamination of Ctenopharynodon idellus that was contaminated by diethylstilbestrol.