Tissue Distribution and Pharmacokinetics of Diethylstilbestrol and Its Metabolite Dienestrol in Ctenopharynodon idellus
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Abstract:
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/(L·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.
