Pharmacokinetics of recombinant activated factor VII in trauma patients with severe bleeding

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dc.contributor.authorKlitgaard, Thomas
dc.contributor.authorTabanera y Palacios, Rene
dc.contributor.authorBoffard, Kenneth
dc.contributor.authorLau, Philip T. C.
dc.contributor.authorWarren, Brian
dc.contributor.authorRizoli, Sandro
dc.contributor.authorRossaint, Rolf
dc.contributor.authorKluger, Yoram
dc.contributor.authorRiou, Bruno
dc.date.accessioned2010-12-14T14:16:44Z
dc.date.available2010-12-14T14:16:44Z
dc.date.issued2006-07
dc.date.updated2010-11-09T13:00:31Z
dc.description.abstractIntroduction: 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 μg.kg-1 after transfusion of eight red blood cell units, followed by additional doses of 100 μg.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.kg-1.h-1; central volume of distribution 89 (32% CV) ml.kg-1; inter-compartmental clearance 24 ml.kg-1.h-1; and peripheral compartment volume 31 ml.kg-1. Baseline FVII coagulant activity was estimated at 0.29 (39% CV) U.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.en_ZA
dc.description.versionPeer Reviewed
dc.format.extent10 p. : ill.
dc.identifier.citationKlitgaard, T, Palacios, RT, Boffard, KD, Lau, PTC, Warren, B, Rizoli, S, Rossaint, R, Kluger, Y, Riou, B & NovoSeven® Trauma Study Group 2006, 'Pharmacokinetics of recombinant activated factor VII in trauma patients with severe bleeding', Critical Care, 10(4):R104.en_ZA
dc.identifier.issn0964-3397
dc.identifier.otherhttp://dx.doi.org/10.1186/cc4977
dc.identifier.urihttp://hdl.handle.net/10019.1/5122
dc.language.isoen_ZAen_ZA
dc.language.rfc3066en
dc.publisherBioMed Centralen_ZA
dc.rights.holderKlitgaard et al.; licensee BioMed Central Ltd.en_ZA
dc.subjectRecombinant activated factor VII (rFVIIa)en_ZA
dc.subjectBleeding in patients with severe traumaen_ZA
dc.subjectPharmacokineticsen
dc.subjectHemorrhage shocken
dc.titlePharmacokinetics of recombinant activated factor VII in trauma patients with severe bleedingen_ZA
dc.typeArticleen_ZA
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