Subchronic toxicity and plasma pharmacokinetic studies on wogonin, a natural flavonoid, in Beagle dogs

Aim of the study: To investigate subchronic toxicity and pharmacokinetic of wogonin using Beagle dog and to provide foundation for clinical applications of this promising anticancer agent. Materials and methods: Wogonin was administered via intravenous infusion at dosages of 60, 30 and 15 mg/kg per day for 90 days followed by subchronic toxicity studies including general body parameters, hematological, plasma biochemical, histopathological, and viscera examinations. Dogs were given single intravenous injection of 20 mg/kg wogonin followed by pharmacokinetic parameters estimating. Results: Dogs treated with wogonin showed no significant changes in organs compared with controls in the toxicological study. An innocuous dose was established to be 60 mg/kg, which was approximately 38.5 (body surface area) times higher than the dose (50 mg/60 kg) used for human trials. The area under concentration-time curve (AUC(infinity)) was estimated to be 2137.9 +/- 231.4 ng h/ml, while the elimination half-life (t(1/2)) was 1.51 +/- 0.43 h in dogs treated with 20 mg/kg wogonin. Conclusions: Wogonin offered a wide margin of safety and had no organ toxicity fora long time intravenous administration in dogs. (C) 2009 Elsevier Ireland Ltd. All rights reserved.