The effects of liver impairment on the pharmacokinetics of brivanib, a dual inhibitor of fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases.
Cancer Chemother Pharmacol
; 72(1): 53-64, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23719718
ABSTRACT
PURPOSE:
Hepatic impairment may impede tyrosine kinase inhibitor metabolism. This phase I study compared the pharmacokinetics of brivanib in patients with hepatocellular carcinoma (HCC) and varying levels of hepatic impairment with those with non-HCC malignancies and normal liver function.METHODS:
Patients were assigned to the following groups Groups A, B, and C (HCC plus mild, moderate, or severe hepatic impairment, respectively) and Group D (non-HCC malignancy and normal hepatic function). Brivanib alaninate (brivanib prodrug) doses were 400 mg in Groups A, B, and D and 200 mg in Group C. Brivanib exposure was determined on day 1 (single dose) and day 28 (multiple doses).RESULTS:
Twenty-four patients participated in the study. After a single brivanib alaninate dose, brivanib exposure was comparable between Groups A, B, and D. Area under the concentration-time curve was 50 % higher in Group C versus Group D. There were not enough data to draw conclusions on multiple doses. Safety profile in Groups A, B, and D was consistent with previous brivanib monotherapy experience. Tolerability could not be assessed in Group C because of dose interruptions and discontinuations, generally due to the disease natural history.CONCLUSIONS:
Brivanib exposure was similar in patients with HCC and mild or moderate hepatic impairment (Child-Pugh [CP] A or B status) and those with non-HCC malignancies and normal hepatic function, suggesting dose adjustment is unnecessary with CP A or B status. Experience with HCC and severe hepatic impairment (CP C status) is insufficient to recommend brivanib use in this population.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triazinas
/
Pró-Fármacos
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Receptores de Fatores de Crescimento de Fibroblastos
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Carcinoma Hepatocelular
/
Receptores de Fatores de Crescimento do Endotélio Vascular
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Insuficiência Hepática
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Alanina
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Fígado
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
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Observational_studies
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Risk_factors_studies
Limite:
Aged80
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos