Pharmacokinetics of a loading dose of intravenous paracetamol post caesarean delivery

Abstract

Background: The postpartum period affects drug disposition, but data of intravenous paracetamol loading dose pharmacokinetics immediately following caesarean delivery have not yet been reported.

Methods: Immediately following caesarean delivery, women received a 2-g loading dose of intravenous paracetamol. Plasma samples were collected at 1, 2, 4 and 6 h. Individual pharmacokinetics were calculated assuming a linear one-compartment model with instantaneous input and first-order output. Data were reported using median and range.

Results: Twenty-eight patients undergoing caesarean delivery were recruited (age 31.5 [20-42] years, weight 79 [57-110] kg, body surface area 1.9 [1.5-2.4]m(2)). Median paracetamol plasma concentrations after 1, 2, 4 and 6 h were 22.5, 15.25, 7.9, and 3.9 mg/L respectively. Paracetamol clearance was 20.3 (11.8-62.8) L/h or 10.9 (7-23.8)L/hm(2), distribution volume 58.3 (42.9-156) L or 0.72 (0.52-1.56) L/kg.

Conclusion: Pharmacokinetics of intravenous paracetamol have been estimated following caesarean delivery. Although limited to a loading dose shortly after surgery, the results are clinically relevant since this is the first description in this patient population. These data provide evidence on which to base further integrated pharmacokinetic/pharmacodynamic studies in peripartum analgesia.