Plenary
Lecture
Clinical pharmacology of non-opoids in young women: the
impact of pregnancy, postpartum and co-medication
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Dr Karel Allegaert
Neonatal Intensive Care Unit
University Hospitals Leuven
BELGIUM
E-mail:
karel.allegaert@uzleuven.be
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).
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