Pharmacokinetic/pharmacodynamic modeling of pegfilgrastim in healthy subjects.
J Clin Pharmacol
; 46(7): 747-57, 2006 Jul.
Article
en En
| MEDLINE
| ID: mdl-16809800
ABSTRACT
This analysis was conducted to characterize the pharmacokinetics and pharmacodynamics of pegfilgrastim and to develop a pharmacokinetic-pharmacodynamic model to describe the granulopoietic effects of pegfilgrastim and the homeostatic regulation of pegfilgrastim clearance in healthy subjects. Pegfilgrastim serum concentration data and differential white cell counts were obtained from an open-label, single-dose, dose escalation study. Healthy subjects (8 subjects/dose group) received a single subcutaneous dose of 30, 60, 100, or 300 microg/kg pegfilgrastim. Pegfilgrastim exhibited nonlinear pharmacokinetics; clearance decreased with increasing dose. A dose-dependent increase in absolute neutrophil count with an increase in the percentage of band cells was observed. A pharmacokinetic-pharmacodynamic model was developed that adequately described the nonlinear pharmacokinetics of pegfilgrastim, feedback regulation of pegfilgrastim clearance by neutrophils, and the differential effects of pegfilgrastim on neutrophil populations in blood.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factor Estimulante de Colonias de Granulocitos
/
Modelos Biológicos
/
Neutrófilos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Clin Pharmacol
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos