2.4 ELIMINATION Triptolide was eliminated quickly with a terminal half-life of approximately 0.42 h after oral administration and 0.19 h by intravenously administration in rats. In dogs, the terminal half-life was 2.5 h after 0.05 mg / kg dosage of triptolide by intravenously [37]. Less than 4 % of parent drug can be detected in male rat feces, urine and bile respectively after 24 h [36, 52]. There is gender-associated discrepancy observed in the eliminated pathway. Comparing with males, only 0.0267 % of triptolide can be detected in female rat urine, while no unchanged parent drug can be found in the feces or bile, which may be attributing to the different types and levels of metabolism enzymes for triptolide [56]. A non-linear kinetics for …show more content…
However, the narrow therapeutic window and multiorgan toxicity has limited it from further clinical use. In order to increase its therapeutic index, different kinds of triptolide-loaded delivery systems have been developed, which has been verified to change the pharmacokinetics of triptolide and decrease the toxicity. The pharmacokinetic study of a triptolide-loaded delivery system in mice showed that a targeted tissue accumulation and longer residence time were found in triptolide-loaded lipid emulsion [62]. The AUC0-t of triptolide-loaded lipid emulsion increased 2.19 folds, suggesting that the triptolide-loaded lipid emulsion does improve the biodistribution, accumulation and therapeutic efficacy in pancreas. Moreover, the levels of triptolide-loaded lipid emulsion in heart, lung and kidney were lower than that of the triptolide group, which would reduce the toxicity of triptolide in the above tissues. A lipid nanoparticled triptolide (a nanoformulation) can significantly increase the AUC, significantly longer tmax and significantly decreased Cmax. Triptolide levels in hepatic, ranal and testicle tissues appear to decrease in the solid lipid nanoparticle. [41]. The triptolide-loaded nanostructured lipid carriers could prolong mean residence time, delayed tmax and decreased Cmax compared to free triptolide and solid lipid nanoparticle, respectively, which was according to the reducing subacute toxicity in male rats