Pharmacokinetics, pharmacodynamics, and safety assessment of palifermin (rHuKGF) in healthy volunteers.
Clin Pharmacol Ther
; 79(6): 558-69, 2006 Jun.
Article
em En
| MEDLINE
| ID: mdl-16765144
ABSTRACT
BACKGROUND:
Palifermin is a recombinant human keratinocyte growth factor approved to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies who received myelotoxic therapy requiring hematopoietic stem cell support.METHODS:
This randomized, double-blind, placebo-controlled study investigated the pharmacokinetics, pharmacodynamics, and safety of palifermin in healthy volunteers after single, escalating doses (60 to 250 mug/kg). Pharmacodynamic measurements (Ki67 staining) assessing buccal mucosal epithelial proliferation were performed at baseline and at 48 or 72 hours after dosing.RESULTS:
Exposure to palifermin increased approximately dose proportionally, with a 3-fold increase observed for a 4-fold increase in dose. Palifermin concentrations decreased sharply during the first 0.5 to 1.5 hours after dosing, slightly increased or plateaued between 1.5 and 6 hours, and subsequently decreased. The overall mean systemic clearance and volume of distribution at steady state were 590 mL/h/kg and 2000 mL/kg, respectively. The mean half-life ranged from 4.5 to 6 hours across the dose levels. The mean and SD ratio of Ki67 staining at 48 hours after dosing to baseline was 1.19 (0.24) for placebo, 2.02 (0.60) for 60 mug/kg, 3.04 (1.13) for 120 mug/kg, and 4.66 (0.77) for 250 mug/kg-treated groups.CONCLUSION:
Palifermin exhibited linear pharmacokinetics and caused dose-dependent epithelial proliferation.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Epiteliais
/
Fator 7 de Crescimento de Fibroblastos
/
Mucosa Bucal
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2006
Tipo de documento:
Article