Pharmacokinetics, tissue distribution, excretion and plasma protein binding studies of wogonin in rats.
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 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.
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24# Tongjiaxiang, Nanjing 210009, Jiangsu, China.
Amer
A
Talbi
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24# Tongjiaxiang, Nanjing 210009, Jiangsu, China.
Di
D
Zhao
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24# Tongjiaxiang, Nanjing 210009, Jiangsu, China.
Qingwang
Q
Liu
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24# Tongjiaxiang, Nanjing 210009, Jiangsu, China.
Junxiu
J
Li
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24# Tongjiaxiang, Nanjing 210009, Jiangsu, China.
Ali
A
Fan
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24# Tongjiaxiang, Nanjing 210009, Jiangsu, China.
Wei
W
Yang
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24# Tongjiaxiang, Nanjing 210009, Jiangsu, China.
Xing
X
Han
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24# Tongjiaxiang, Nanjing 210009, Jiangsu, China. chenxj-lab@hotmail.com.
Xijing
X
Chen
D000818:Animals; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism*; D044950:Flavanones / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011485:Protein Binding; D051381:Rats; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
D001798:Blood Proteins; D044950:Flavanones; C085514:wogonin