Population pharmacokinetics of farletuzumab, a humanized monoclonal antibody against folate receptor alpha, in epithelial ovarian cancer.
Cancer Chemother Pharmacol
; 70(5): 727-34, 2012 Nov.
Article
en En
| MEDLINE
| ID: mdl-22955257
ABSTRACT
PURPOSE:
The purpose of this analysis was to develop a population pharmacokinetic model for farletuzumab, a humanized immunoglobulin (Ig)G(1) monoclonal antibody (mAb) to the folate receptor alpha, which is a receptor over-expressed in ovarian cancer, but largely absent from normal tissue.METHODS:
In total, 2,472 samples were included in the building of the pharmacokinetic model. Farletuzumab 12.5-400 mg/m(2) had been administered via intravenous infusion to 79 patients with advanced ovarian cancer enrolled in one of the two clinical studies. Data were analyzed by a nonlinear mixed-effects modeling approach.RESULTS:
Farletuzumab pharmacokinetics was best described by a two-compartment model with first-order (linear) elimination. In the final model, estimated values of clearance and volume of distribution of the central compartment were 0.00784 l/h and 3.00 l, respectively. Body weight was the only covariate investigated that explained inter-patient variability in clearance and the central volume of distribution. There was no effect of age, human anti-human antibodies, or concomitant chemotherapy on the pharmacokinetics of farletuzumab. Simulations showed that, when the mg/kg/week dose was maintained, steady-state exposure to farletuzumab was similar with dosing every week or every 3 weeks.CONCLUSIONS:
The pharmacokinetic parameters of farletuzumab are similar to those of other IgG mAbs. The results support weight-based dosing of farletuzumab on a weekly or 3-weekly schedule.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Neoplasias Glandulares y Epiteliales
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Anticuerpos Monoclonales Humanizados
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Modelos Biológicos
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Antineoplásicos
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos