RESUMEN
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 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 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.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antineoplásicos/farmacocinética , Diterpenos/farmacología , Microsomas Hepáticos/efectos de los fármacos , Niacinamida/análogos & derivados , Fenantrenos/farmacología , Compuestos de Fenilurea/farmacocinética , Inhibidores de Proteínas Quinasas/farmacocinética , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/sangre , Antineoplásicos/metabolismo , Biotransformación/efectos de los fármacos , Células CACO-2 , Citocromo P-450 CYP3A/química , Citocromo P-450 CYP3A/metabolismo , Inhibidores del Citocromo P-450 CYP3A/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Enterocitos/efectos de los fármacos , Enterocitos/metabolismo , Compuestos Epoxi/farmacología , Femenino , Semivida , Humanos , Absorción Intestinal/efectos de los fármacos , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/metabolismo , Niacinamida/administración & dosificación , Niacinamida/sangre , Niacinamida/metabolismo , Niacinamida/farmacocinética , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/sangre , Compuestos de Fenilurea/metabolismo , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/sangre , Inhibidores de Proteínas Quinasas/metabolismo , Ratas Sprague-Dawley , SorafenibRESUMEN
BACKGROUND: Epidemiological studies evaluating the association between vitamin E intake and glioma risk have produced inconsistent results. Thus, we conducted a meta-analysis to summarize the evidence from epidemiological studies of vitamin E intake with the risk of glioma. METHODS: Pertinent studies were identified by a search in pubmed and web of knowledge up to August 2014. The random-effect model was used to combine the results. Publication bias was estimated using the Egger's regression asymmetry test. RESULTS: Twelve studies including 3180 glioma cases about vitamin E intake with the risk of glioma were included in this meta-analysis. The combined relative risk (RR) of glioma associated with vitamin E intake was 0.88 (95% CI = 0.69-1.12). The association was significant neither in the case-control studies nor in the cohort studies. No publication biases were found. CONCLUSIONS: Our analysis indicated that vitamin E intake is not associated with the risk of glioma.