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Population PK Modeling of Plasma Derived Coagulation Factor IX
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Farmakokinetik och farmakodynamik)
2011 (English)Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

The aims of this project were to first develop a population pharmacokinetic

model of plasma derived coagulation factor IX and secondly to investigate if

coagulation factor IX has 3-compartment pharmacokinetics rather than

2-compartment pharmacokinetics. A total of 999 plasma samples along with

the patient characteristics bodyweight, age and factor IX preparation from 26

patients served as data for the project. Population pharmacokinetic curve

fitting was performed by means of NONMEM 6. Clotting factor IX had

3-compartment pharmacokinetics rather than 2-compartment pharmacokinetics.

This allowed for the computation of the three half-lives. The typical value

terminal half-life for coagulation factor IX was shorter than published mean

values of 29-43 hours, while the terminal half-lives for individual patients were

well within the interval of reported terminal half-lives. The new model shows

that inter-occasion variance is lower than inter-individual variance, which is a

requirement for pharmacokinetic based dosing. Model performance was evaluated

using tools for model diagnostics. Goodness of fit plots along with calculations

of epsilon and eta shrinkage showed good fit with low shrinkage. Visual

predictive check indicated excellent performance of the 3-compartment model

of clotting factor IX. The development of the first population pharmacokinetic

model of plasma derived coagulation factor IX and the estimations of variance

and pharmacokinetic parameters allows for treatment optimization through

multiple-dose simulations, optimization of sampling for determination of

individual pharmacokinetics and statistical support for pharmacokinetic based


Place, publisher, year, edition, pages
2011. , 24 p.
UPTEC K, ISSN 1650-8297 ; 11026
National Category
Pharmacology and Toxicology
URN: urn:nbn:se:uu:diva-179064OAI: oai:DiVA.org:uu-179064DiVA: diva2:543194
Subject / course
Pharmaceutical Biosciences
Educational program
Master Programme in Chemical Engineering
Available from: 2012-10-05 Created: 2012-08-07 Last updated: 2012-11-19Bibliographically approved

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Åhlén, Victor
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