Background and Goal of Study: Pregnancy affects intravenous (iv) paracetamol pharmacokinetics (1), but there are no studies on covariates of iv paracetamol pharmacokinetics within a pregnant population.
Materials and Methods: Shortly following caesarean section, women received a loading dose (2 g) of iv paracetamol and 4 (1, 2, 4 and 6 h) plasma samples were collected and analysed with an earlier reported HPLC technique (2). Individual pharmacokinetics were calculated assuming a linear one compartment model with instantaneous input, first order output. Covariates of between subject variability (preterm vs term, maternal disease vs healthy, twin vs singleton) within this cohort were explored (Mann Whitney U).
Results and Discussion: Pharmacokinetics were calculated for 34 patients. 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).
Conclusion(s): 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.
1. Kulo A, et al. Int J Obstet Anesth (in press)
2. Allegaert K, et al. Eur J Clin Pharmacol 2004;60:191-197