The Effects of Triptolide on the Pharmacokinetics of Sorafenib in Rats and Its Potential Mechanism

Overview

Journal Pharm Biol

Specialties Pharmacology
Pharmacy

Date 2017 Jun 16

PMID 28614959

Citations 19

Authors

Xianming Wang

Xin Zhang

Fei Liu

Minghai Wang

Shiyong Qin

Affiliations

Soon will be listed here.

Abstract

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 (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 of sorafenib increased significant (p < 0.05) from 9.02 ± 1.16 to 12.17 ± 2.95 h at low dose with the pretreatment of triptolide. Triptolide has little effect on the absorption of sorafenib in Caco-2 cell transwell model. However, triptolide could significantly decrease the intrinsic clearance rate of sorafenib from 51.7 ± 6.37 to 32.4 ± 4.43 μL/min/mg protein in rat liver microsomes.

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.

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Zaafar D, Khalil H, Rasheed R, Eltelbany R, Zaitone S PLoS One. 2022; 17(8):e0271631.

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Pharmacokinetic Drug Interaction Study of Sorafenib and Morphine in Rats.

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PMID: 34959453 PMC: 8707786. DOI: 10.3390/pharmaceutics13122172.

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