Tamara van Donge

Chapter 2 26 Pregnancy and pharmacotherapy: something to worry about? During pregnancy, women take a variety of medications (either prescribed or over-the counter) which can have negative impacts on the pregnant woman and her unborn child. Antenatal medication use during pregnancy has increased over the last three decades. 4 On the other hand, recent study showed that women of child-bearing age in Switzerland have high general health awareness and when they become pregnant, most of them refrain from using pain killers. 5 Surveys about their medication use have illustrated that the percentage of pregnant women who took pain killers once a week to several times a week was about half of that in non-pregnant women (25% vs 50%). Of note, in 67% of pregnant women using pain killers, these were prescribed by a physician, as compared to 35% in non-pregnant women. 5 Pregnancy affects various physiological processes and alters the body composition of the pregnant woman. These changes can affect the pharmacokinetics of drugs and should therefore be taken into account when prescribing drugs and may even require dosing adjustments to ensure appropriate treatment. 6 A recent review investigated the alterations in pharmacokinetics during pregnancy studying 121 different medications based on 198 studies in pregnant women. 7 Enhanced elimination, resulting in decreased drug exposure at a given dose, was one of the main conclusions. Alterations in drug absorption (k a ) are caused by altered bioavailability and delayed time to reach peak levels after oral administration, which are due to decreased gastrointestinal motility and increased gastric pH (Figure 1). 8 For hydrophilic drugs, the volume of distribution (V d ) is increased because of increased total body water and plasma volume, whereas V d for hydrophobic drugs is increased because of a larger fat compartment. Clearance of drugs is influenced by many processes such as altered glomerular filtration rate and an adjusted cardiac output. 7 Furthermore, diminished plasma albumin concentrations during pregnancy may increase free, and therefore active drug concentrations which is associated with a potential increase in drug activity, depending on the physiochemical characteristics of the given drug. 7 Unfortunately, for a majority of drugs used during pregnancy, information regarding pharmacokinetic (PK) changes and related effects on safety and efficacy is still lacking. Physiology-based pharmacokinetics (PBPK) models are increasingly utilized to characterize changes in pharmacokinetics during pregnancy. 6 In such mechanistic models, physiological parameters (e.g. organ volumes, glomerular filtration rate) are combined with drug-specific parameters (e.g. lipophilicity, molecular mass) and this ensures the assessment of valuable insights into the PK profiles of drugs in this specific population. 9 The prediction of drug exposure could contribute to the adjustment of dosing regimen for drugs prescribed in pregnant women. PBPK modeling can also be deployed to understand effects of concomitantly interacting drugs, which is often the case for HIV infected women because