LAUSR

Abstract 1. Dihydromyricetin (DMY) has anti-tumor and hepatoprotective activities and inhibits the activity of CYP enzymes and P-gp. In this research, we explored the effect of DMY on the pharmacokinetics of triptolide (TP), an anti-tumor Chinese medicine that is mainly metabolized by CYP enzymes and is the substrate of P-gp. 2. Rats were administrated TP (1.2 mg/kg) with and without DMY in different dosage regimens, then a sensitive and reliable LC–MS/MS method was developed and applied to assess the pharmacokinetics of TP. The blood samples for TP were collected from each rat up to 120 min after administration of TP. 3. When co-administrated with single dose of DMY (100 mg/kg), the AUC, Cmax and T1/2 of TP were significantly enhanced by 98, 83 and 66%, respectively. The T1/2 of TP was significantly prolonged from 23.6 ± 6.4 to 70.5 ± 12.5 min with 14-doses pretreatment of DMY (500 mg/kg), conversely, the Cmax was decreased by 30% and the AUC was enhanced by 24%. 4. These results hinted that administration of DMY with TP did alter the pharmacokinetics of TP, and provided the theoretical pharmacokinetic basis to study on the protective effects of DMY against acute liver injury caused by TP.