Abstract: To assess potential pregnancy related changes, iv loading dose (2 g) pararcetamol pharmacokinetics shortly following caesarean section were collected and compared to a similar dataset of 14 female healthy volunteers. Individual pharmacokinetics were calculated assuming a linear one compartment model with instantaneous input, first order output.). Median clearance (15.5 vs 20.3 l/h, p<0.01) and distribution volume (43.7 vs 58.3 L, p<0.001) were significantly higher post caesarean section. Even after correction for body surface area, this increase in clearance (9.6 vs 10.9 l/h.m³) remained significant (p<0.05). Immediately following cesarean, paracetamol clearance (+35%) and distribution volume (+30%) are increased compared to healthy adult volunteers. When further focusing on within pregnancy differences, covariates of between subject variability (preterm vs term, maternal disease vs healthy, twin vs singleton) within this cohort were explored (Mann Whitney U). Median clearance was 20.3 (11.8-62.8) l/h or - when corrected for body surface area – 10.9 (range 7-28.3) l/h.m². No significant effect of twin (n=8) pregnancy or maternal co-morbidity (n=3) was observed, but median clearance after preterm delivery (n=12, <37 weeks gestational age) was significantly higher (23.2 vs 19.8 l/h and 12.6 vs 10.2 l/h.m², both p<0.05) compared to term (n=22) delivery. Similarly, there was a difference in median distribution volume (0.75 vs 0.69 l/kg, p<0.05), resulting in the absence of differences in median elimination half life (108 vs 119 min). Women who underwent a preterm caesarean had a higher paracetamol clearance compared to term cases. Consequently, we suggest to reconsider iv paracetamol dosing, with potential additional value to either use higher doses or shorter time intervals in preterm cases. We encourage caregivers to perform similar within-pregnancy studies for other drugs administered in this population because of absence of pharmacokinetic data.

Brief biography of the speaker:
Karel Allegaert, MD, PhD graduated from the Katholieke Universiteit Leuven as medical doctor (1994), with a subsequent training in Pediatrics/Neonatology (2001) and Clinical Pharmacology (2005). Following the presentation of his PhD defence (neonatal analgesia: towards an integrated approach), he further combined clinical care as a consultant of the neonatal intensive care unit, University Hospitals Leuven with clinical research with specific emphasis on perinatal clinical pharmacology (special populations, including preterm neonates and pregnancy). He was appointed as associated professor of the Katholieke Universiteit Leuven in 2005, and subsequently further developed these research activities, currently reflected in about 200 publications in national and international journals, conference proceedings and chapters in book. His clinical research has (FWO clinical doctoral grant) and still is supported by a Fundamental Clinical Investigatorship (2009-2013) of the FWO Vlaanderen. This research also resulted in several awards of the Belgian Academy of Medicine and Sciences (Govaerts award for Clinical Toxicology 2006-2008, and Heymans Award Clinical Pharmacology 2002-2004), the Belgian Pain Society (2005),and the Galenus price, clinical research pharmacology, Belgium (2009).