Program

Clinical pharmacology during pregnancy: Another special population in search of evidence based dosing

[Speaker] Karel Allegaert:1
1:Department of Development and Regeneration, KU Leuven, Belgium and Erasmus MC, the Netherlands

The general pharmacokinetic principles of disposition and elimination of exogenous compounds apply, irrespective of population specific characteristics. However, pregnancy and delivery warrant a focused approach because important alterations in physiology (e.g. renal, hepatic, metabolism, body composition) affect drug disposition up to the level of clinical relevance.
During pregnancy, there are changes in distribution volume due to changes in body composition, in metabolic activity affecting drug metabolism and in renal elimination (GFR, tubular) capacity. The link between pregnancy related changes in medical physiology and changes in drug disposition will be illustrated based on aspects of cefazolin, ketorolac and paracetamol dispositions during pregnancy and after delivery. Beyond these anecdotal observations, patterns related to medical physiology are unveiled. Moreover, pregnancy is not a dichotomous variable.
Pregnancy and postpartum can be considered as another special population, but physiology-based pharmacokinetic model development, the development of large and high quality epidemiological datasets are key issues. Finally, and similar to neonates or infants, drug development plans should also focus on specific pregnancy related diseases (pre-eclampsia, hyperemesis, preterm labor, fetal diseases) beyond generating information on already available drugs. Repurposing like for sildenafil to treat growth restriction or other fetal diseases is a nice illustration of a 'go' between approaches, redeveloping an already existing drug for another pregnancy related disease.
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