Population pharmacokinetic analyses of the effect of carboplatin pretreatment on olaparib in recurrent or refractory women's cancers.
Cancer Chemother Pharmacol
; 80(1): 165-175, 2017 Jul.
Article
en En
| MEDLINE
| ID: mdl-28577239
ABSTRACT
PURPOSE:
Combining olaparib with carboplatin was recently shown to be active in both BRCA and non-BRCA mutant cancers in a recent phase I/Ib combination trial. The optimal drug sequence recommended was carboplatin 1-day before olaparib. However, carboplatin pre-treatment induced a ~50% faster olaparib clearance.METHODS:
To further explore this drug interaction, a population pharmacokinetic (PK) model was designed that included a lag time parameter, a second absorption compartment from tablet formulation, a single distribution/elimination compartment, and covariance among the clearance and volume parameters.RESULTS:
Clearance (6.8 L/h) and volume (33 L) estimates were comparable with literature. The only significant covariate was the presence of carboplatin on olaparib clearance, consistent with published noncompartmental PK and in vitro data.CONCLUSIONS:
Simulations predicted lower steady-state peak/trough olaparib exposure through 24-36 h post carboplatin pre-treatment, but this effect was lost by day 2 and thus no dose adjustment is recommended.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ftalazinas
/
Piperazinas
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Carboplatino
/
Modelos Biológicos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Aged
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Female
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Humans
/
Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos