Plasma and cerebrospinal fluid pharmacokinetics of MP470 in non-human primates.
Cancer Chemother Pharmacol
; 67(4): 809-12, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-20563581
ABSTRACT
PURPOSE:
MP470 is a multi-targeted tyrosine kinase inhibitor with potent activity against mutant c-Kit, PDGFRα, Flt3, c-Met and c-Ret that is being evaluated as an anticancer agent. The plasma and cerebrospinal fluid (CSF) pharmacokinetics of MP470 were studied in a non-human primate model that is highly predictive of CSF penetration in humans.METHODS:
Oral MP470, 300 mg, was administered to four non-human primates. Serial samples of blood were collected from four animals and CSF samples from three animals for pharmacokinetic studies. Plasma and CSF concentrations were measured using an LC-MS/MS assay. Both model-independent and model-dependent methods were used to analyze the pharmacokinetic data.RESULTS:
Following a one-time oral dose of 300 mg, the MP470 plasma area under the curve (AUC) was 1,690 ± 821 nM h (mean ± SD). The half-life of MP470 in the plasma was 11.0 ± 3.4 h. There was no measurable MP470 in the CSF.CONCLUSIONS:
Although CSF penetration is minimal, MP470 has demonstrated potent activity against cancer cell lines in vitro and in vivo, and further clinical investigation is warranted.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirimidinas
/
Inhibidores de Proteínas Quinasas
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos