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 20mg/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 (50mg/60 kg) used for human trials. The area under concentration-time curve (AUC(infinity)) was estimated to be 2137.9+/-231.4 ngh/ml, while the elimination half-life (t(1/2)) was 1.51+/-0.43 h in dogs treated with 20mg/kg wogonin. CONCLUSIONS Wogonin offered a wide margin of safety and had no organ toxicity for a long time intravenous administration in dogs.