Pharmacokinetics of recombinant activated factor VII in trauma patients with severe bleeding.
Crit Care
; 10(4): R104, 2006.
Article
em En
| MEDLINE
| ID: mdl-16859505
ABSTRACT
INTRODUCTION:
Recombinant activated factor VII (rFVIIa) has been used as adjunctive therapy in trauma patients with severe bleeding. However, its pharmacokinetics profile remains unknown.METHODS:
In two placebo-controlled studies in patients with blunt and penetrating trauma, the pharmacokinetics of rFVIIa given at an initial dose of 200 microg x kg-1 after transfusion of eight red blood cell units, followed by additional doses of 100 microg x kg-1, one and three hours later, have been studied, based on the FVII coagulant activity assay. Both non-compartment and population pharmacokinetic analyses were performed. A two-compartment, population pharmacokinetic model was used to estimate a population profile for the rFVIIa dosing regimen. Data are population means (percent coefficient of variation (CV)).RESULTS:
Based on the two-compartment population model, the estimated pharmacokinetic parameters were clearance 40 (30% CV) ml x kg-1 x h-1; central volume of distribution 89 (32% CV) ml x kg-1; inter-compartmental clearance 24 ml x kg-1 x h-1; and peripheral compartment volume 31 ml x kg-1. Baseline FVII coagulant activity was estimated at 0.29 (39% CV) U x ml-1, initial half-life was 0.6 (34% CV) hours, and terminal half-life 2.4 (50% CV) hours. High intra- and inter-patient variability was noted in volume of distribution and clearance, which was in part correlated with the transfusion requirements as the single significant covariate. The non-compartmental analysis led to almost identical estimates of key parameters.CONCLUSION:
A high intra- and inter-patient variability was noted in the volume of distribution and clearance of rFVIIa in trauma patients with severe bleeding, mainly related with the transfusion requirements and thus blood loss and/or bleeding rate.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ferimentos não Penetrantes
/
Ferimentos Penetrantes
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Fator VII
/
Hemorragia
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
/
Female
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Humans
/
Male
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article