A Bayesian population PK-PD model of ispinesib-induced myelosuppression.
Clin Pharmacol Ther
; 81(1): 88-94, 2007 Jan.
Article
en En
| MEDLINE
| ID: mdl-17186004
The goal of the present analysis is to fit a Bayesian population pharmacokinetic pharmacodynomic (PK-PD) model to characterize the relationship between the concentration of ispinesib and changes in absolute neutrophil counts (ANC). Ispinesib, a kinesin spindle protein (KSP) inhibitor, blocks assembly of a functional mitotic spindle, leading to G2/M arrest. A first time in human, phase I open-label, non-randomized, dose-escalating study evaluated ispinesib at doses ranging from 1 to 21 mg/m(2). PK-PD data were collected from 45 patients with solid tumors. The pharmacokinetics of ispinesib were well characterized by a two-compartment model. A semimechanistic model was fit to the ANC. The PK and PD data were successfully modelled simultaneously. This is the first presentation of simultaneously fitting a PK-PD model to ANC using Bayesian methods. Bayesian methods allow for the use of prior information for some system-related parameters. The model may be used to examine different schedules, doses, and infusion times.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Quinazolinas
/
Benzamidas
/
Teorema de Bayes
/
Neutropenia
/
Antineoplásicos
Tipo de estudio:
Clinical_trials
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Health_economic_evaluation
/
Prognostic_studies
Límite:
Adult
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Aged
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Aged80
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Clin Pharmacol Ther
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos