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

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 successfully 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.