Abstract: AIM: To explore the toxicokinetic properties of triptolide in Beagle dogs after oral and intravenous administration and to observe it's toxicity for providing the further information of deeply investigating the mechanism of triptolide. METHODS: 25 Beagle dogs were divided into five groups, group A(0.1 mg/kg), group B(0.08 mg/kg), group C(0.05 mg/kg) by oral administration, group D(0.08 mg/kg)by intravenous administration and group E for blank control, respectively. These dogs were dosed continually for 14 days. The plasma/serum or tissue samples were collected for toxicokinetic analysis and toxic evaluation including routine biochemical assays and histopathological inspection. RESULTS: Comparing the PK parameters on Day 1, there were some changes on Day 14 after exposing to triptolide for 14 days either oral or intravenous administration. AUC_0-∞ and C_max were increased from 145.86 to 276.24 ng·h·mL^-1 and from 44.49 to 75.26 ng/mL respectively after intravenous administration of 0.08 mg/kg triptolide; For oral administration, AUC_0-∞ and C_max were increased from 151.54 to 289.98 ng·h·mL^-1 and from 44.49 to 75.26 ng/mL at the dose of 0.1 mg/kg, from 37.78 to 61.65 ng·h·mL^-1 and from 44.49 to 75.26 ng/mL at the dose of 0.08 mg/kg, from 67.92 to 143.98 ng·h·mL^-1 and from 24.05 to 38.07 ng/mL at the dose of 0.05 mg/kg. MRT and T_1/2 was also longer on Day 14 than on Day 1. The observation of toxicity indicated that it was dose and time dependent, which was showed various level of gastro-intestinal reaction, liver impairments and decreased amount of white cells. CONCLUSION: It was estimated that the gastrointestinal tract and liver were the targeted toxic organs and the administration way was expected to impact the safety of triptolide in dogs.

Key words: toxicokinetics, triptolide, toxicity