Leveraging physiological data from literature into a pharmacokinetic model to support informative clinical study design in pregnant women

van Hasselt, J. G. Coen, Green, Bruce and Morrish, Glynn A. (2012) Leveraging physiological data from literature into a pharmacokinetic model to support informative clinical study design in pregnant women. Pharmaceutical Research, 29 6: 1609-1617. doi:10.1007/s11095-012-0671-2


Author van Hasselt, J. G. Coen
Green, Bruce
Morrish, Glynn A.
Title Leveraging physiological data from literature into a pharmacokinetic model to support informative clinical study design in pregnant women
Journal name Pharmaceutical Research   Check publisher's open access policy
ISSN 0724-8741
1573-904X
Publication date 2012-06-01
Sub-type Article (original research)
DOI 10.1007/s11095-012-0671-2
Volume 29
Issue 6
Start page 1609
End page 1617
Total pages 9
Place of publication New York, United Kingdom
Publisher Springer New York
Collection year 2013
Language eng
Formatted abstract
Purpose: Physiological changes during pregnancy can effect pharmacokinetic (PK) parameters, which may lead to altered dose requirements. We aimed to leverage literature-based physiological changes during pregnancy into a PK model and compare its performance to a published reference model in pregnant women and to use the literature-based model to determine informative PK sampling times for a clinical study that aims to quantify the PK of enoxaparin throughout pregnancy.
Methods: Changes in total body water (BW) and creatinine clearance (CRCL) during pregnancy were described using regression models. BW and CRCL were linked to a PK model of enoxaparin in non-pregnant women. Performance of the literature-based PK model was compared to a previously published empirical reference model. D-optimal sampling times were determined and evaluated for literature-based and reference models. Results: The literature-based model adequately predicted anti-Xa plasma concentrations when compared to reference model predictions. An informative sampling design was succesfully developed, with parameters expected with good precision (RSE < 36.4%). Conclusion: A literature-based model describing enoxaparin PK during pregnancy was developed and evaluated. The modelling framework could be used to support development of informative designs in pregnancy when prior models are unavailable.
Keyword Enoxaparin
NONMEM
Optimal design
Pharmacokinetics
Pregnancy
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
School of Pharmacy Publications
 
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