The effects of triptolide on the pharmacokinetics of sorafenib in rats and its potential mechanism.
Pharm Biol
; 55(1): 1863-1867, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-28614959
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 ANDMETHODS:
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 Cmax (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 t1/2 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 ANDCONCLUSIONS:
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.Palavras-chave
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MEDLINE
Assunto principal:
Fenantrenos
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Compostos de Fenilureia
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Microssomos Hepáticos
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Niacinamida
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Inibidores de Proteínas Quinases
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Diterpenos
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Antineoplásicos
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Antineoplásicos Fitogênicos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article