Pharmacokinetics, Tissue Distribution, Excretion and Plasma Protein Binding Studies of Wogonin in Rats
AbstractWogonin is a natural anticancer candidate. The purpose of this study was to explore the pharmacokinetic profiles, tissue distribution, excretion and plasma protein binding of wogonin in Sprague—Dawley rats. A rapid, sensitive, and specific LC-MS/MS method has been developed for the determination of wogonin in different rat biological samples. After i.v. dosing of wogonin at different levels (10, 20 and 40 mg/kg) the elimination half-life was approximately 14 min, the AUC0-∞ increased in a dose disproportional manner from 112.13 mg/L·min for 10 mg/kg to 758.19 mg/L·min for 40 mg/kg, indicating a non linear pharmacokinetic profile. After i.g. dosing at 100 mg/kg, plasma levels of wogonin peaked at 28 min with a Cmax value of 300 ng/mL and a very low oral bioavailability (1.10%). Following i.v. single dose (20 mg/kg), wogonin was detected in all examined tissues (including testis) with the highest levels in kidney and liver. Approximately 21% of the administered dose was excreted as unchanged drug (mainly via non-biliairy fecal route (16.33%). Equilibrium dialysis was used to evaluate plasma protein binding of wogonin at three concentrations (0.1, 0.5 and 2 µg/mL). Results indicated a very high protein binding degree (over 90%), reducing substantially the free fraction of the compound.
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Talbi, A.; Zhao, D.; Liu, Q.; Li, J.; Fan, A.; Yang, W.; Han, X.; Chen, X. Pharmacokinetics, Tissue Distribution, Excretion and Plasma Protein Binding Studies of Wogonin in Rats. Molecules 2014, 19, 5538-5549.
Talbi A, Zhao D, Liu Q, Li J, Fan A, Yang W, Han X, Chen X. Pharmacokinetics, Tissue Distribution, Excretion and Plasma Protein Binding Studies of Wogonin in Rats. Molecules. 2014; 19(5):5538-5549.Chicago/Turabian Style
Talbi, Amer; Zhao, Di; Liu, Qingwang; Li, Junxiu; Fan, Ali; Yang, Wei; Han, Xing; Chen, Xijing. 2014. "Pharmacokinetics, Tissue Distribution, Excretion and Plasma Protein Binding Studies of Wogonin in Rats." Molecules 19, no. 5: 5538-5549.