Does pregnancy affects intravenous paracetamol disposition? a paired analysis

摘要

To compare intravenous (iv) paracetamol (acetaminophen) pharmacokinetics during pregnancy and postpartum, iv 2g loading paracetamol dose was administered to 8 women, both immediately following a Caesarean section and at least 6 weeks after delivery. Noncompartmental PK model and intraindividual comparison were undertaken. Most PK parameters were significantly different between both periods. Both absolute clearance and clearance corrected for body surface area (BSA(), as well as volume of distribution were significantly higher in pregnant compared to postpartum state resulting in only slight increase in elimination half-life. Higher amount of paracetamol-glucuronide excreted in 6h urine and higher paracetamol glucuronide:sulpfate ratio suggested glucuronidation to be enhanced during pregnancy. The renal clearance of unchanged paracetamol did not differ between both visits. Based on the estimates obtained, further focussed studies on pharmacokinetics during pregnancy and in postpartum are needed.