The physiological changes of pregnancy alter the pharmacokinetics of low molecular weight heparins (LMWH). The optimal dosing strategy of LMWH for the treatment of antenatal venous thromboembolism (VTE) is not known and this has led to significant variation in prescribing practice when women are managed for antenatal VTE with LMWH. The aim of this thesis is to describe the pharmacokinetics of enoxaparin during pregnancy using the method of population pharmacokinetic (PK) modelling. In addition, pregnant women’s thrombin generation and D-dimers are measured and described and their views and adherence to enoxaparin are explored. Pregnant women prescribed enoxaparin at King’s College Hospital were eligible for recruitment. Subjects (n=123) had up to 3 anti-Xa activities drawn per clinic visit (monthly), contributing 795 anti-Xa activities for PK modelling purposes. A one compartment model, with a combined error model, produced a robust enoxaparin antenatal PK model, with weight, baseline lean body weight and gestation found to be significant covariates on enoxaparin antenatal PK. Simulations from the final PK model revealed that a once daily dose of enoxaparin is appropriate in this setting. D-dimer concentrations were found to increase in line with gestation (r=0.382). Thrombin generation was also increased during the antenatal period, with enoxaparin found to influence the different thrombin generation parameters in a dose-dependent manner. Findings from the adherence aspect of this study revealed that women were highly adherent to enoxaparin antentally (mean 97.92%) and demonstrates that women are prepared to inject themselves with a parenteral medication, if they feel it is protecting theirs and their unborn baby’s health; this belief does impact on adherence to LMWH during the postnatal period, where in some women adherence drops (mean 92.75%). This study describes the pharmacokinetic profile of enoxaparin during pregnancy and provides compelling evidence for enoxaparin once daily dosing for managing antenatal VTE.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:677100 |
| Date | January 2015 |
| Creators | Patel, Jignesh |
| Contributors | Davies, John Graham |
| Publisher | King's College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://kclpure.kcl.ac.uk/portal/en/theses/population-pharmacokinetics-of-enoxaparin-during-the-antenatal-period(4a274f3a-b666-4d84-b8a0-2b10106a5b3e).html |
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