Subchronic toxicity and plasma pharmacokinetic studies on wogonin, a natural flavonoid, in Beagle dogs.
OBJECTIVE
To investigate subchronic toxicity and pharmacokinetic of wogonin using Beagle dog and to provide foundation for clinical applications of this promising anticancer agent.


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.
Peng
Jian
J
Key Laboratory for Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
Qi
Qi
Q
You
Qidong
Q
Hu
Rong
R
Liu
Wenyuan
W
Feng
Feng
F
Wang
Guangji
G
Guo
Qinglong
Q
D000469:Alkaline Phosphatase / Q000097:blood; D000825:Animal Structures; D000818:Animals; D019540:Area Under Curve; D001773:Blood Cells; D001806:Blood Urea Nitrogen; D002784:Cholesterol / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D044950:Flavanones / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D006207:Half-Life; D006403:Hematologic Tests; D007275:Injections, Intravenous; D023421:Models, Animal; D009929:Organ Size / Q000187:drug effects; D018517:Plant Roots; D031364:Scutellaria baicalensis; D014280:Triglycerides / Q000097:blood
D004365:Drugs, Chinese Herbal; D044950:Flavanones; D014280:Triglycerides; D002784:Cholesterol; D000469:Alkaline Phosphatase; C085514:wogonin