Pharmacokinetics, Tissue Distribution, Excretion and Plasma Protein Binding Studies of Wogonin in Rats

Molecules

Amer Talbi¹  Di Zhao¹  Qingwang Liu²  Junxiu Li²  Ali Fan²  Wei Yang²  Xing Han² 

[1] id="af1-molecules-19-05538">Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24# Tongjiaxiang, Nanjing 210009, Jiangsu, Chi

关键词: flavonoids;    excretion;    LC-MS/MS;    Scutellaria baicalensis Georgi;    wogonin;   

DOI  :  10.3390/molecules19055538

来源: mdpi

【 摘 要 】

Wogonin 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 AUC_0-∞ 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 C_max 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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.