The effects of triptolide on the pharmacokinetics of sorafenib in rats and its potential mechanism

Context: Combining sorafenib with triptolide could inhibit tumour growth with greater efficacy than single-agent treatment. However, their herb–drug interaction remains unknown.

Objective: This study investigates the herb–drug interaction between triptolide and sorafenib.

Materials and methods: The effects of triptolide (10?mg/kg) on the pharmacokinetics of different doses of sorafenib (20, 50 and 100?mg/kg) in rats, and blood samples were collected within 48?h and evaluated using LC-MS/MS. The effects of triptolide on the absorption and metabolism of sorafenib were also investigated using Caco-2 cell monolayer model and rat liver microsome incubation systems.

Results: The results showed that the C_max (low dose: 72.38?±?8.76 versus 49.15?±?5.46?ng/mL; medium dose: 178.65?±?21.05 versus 109.31?±?14.17?ng/mL; high dose: 332.81?±?29.38 versus 230.86?±?9.68?ng/mL) of sorafenib at different doses increased significantly with the pretreatment of triptolide, and while the oral clearance rate of sorafenib decreased. The t_1/2 of sorafenib increased significant (p?Discussion and conclusions: These results indicated that triptolide could change the pharmacokinetic profiles of sorafenib in rats; these effects might be exerted via decreasing the intrinsic clearance rate of sorafenib in rat liver.