Population pharmacokinetic modeling of recombinant factor IX: Development of non-linear mixed effect model
Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
Introduction: Hemophilia B may be treated by administration of recombinant coagulation factor IX. At the moment the only registered drug for this indication is BeneFix® (Genetics Institute). Prophylaxis has shown to be the optimal treatment with a high success rate and is preferred over intermittent treatment. This study was a continuation of a previously published study concerning the pharmacokinetics of recombinant factor IX. Aim: The primary aim of the study was to develop a population pharmacokinetic model for recombinant factor IX by using non-linear mixed effect modeling software NONMEM. The secondary aim was to develop a simple method for finding initial estimates for the NONMEM model. Material and Methods: The modeling process used a stepwise model building method based on previous method for plasma-derived factor IX. This method used mainly scripting with Perl and the module Perl-speaks-NONMEM as the main tools. Optimal design with Federov exchange algorithm was used to create a method for finding initial estimations. Results: The final model used 3-compartment structural model, combined additive and proportional residual error model, interindividual variance (4 η) and first order conditional estimation with interaction. Allometric scaling was concluded as necessary although the optimal allometric scaling model could not be determined. Age was identified as a covariate on V3. Conclusions: The final model was not the optimal model but the predictions may still be clinically relevant for recombinant factor IX.
Place, publisher, year, edition, pages
2013. , 36 p.
population pharmacokinetics, recombinant factor IX, hemophilia B, BeneFix, NONMEM, modeling, non-linear mixed effect model
IdentifiersURN: urn:nbn:se:uu:diva-192971OAI: oai:DiVA.org:uu-192971DiVA: diva2:600908
Subject / course
Björkman, Sven, Professor
Hammarlund-Udenaes, Margareta, Professor