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

摘要

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.