Pharmacokinetics of Oxycodone in Labouring Women With Preliminary Estimates of Neonatal Exposure
P. Välitalo(1), M. Kokki(2), F. Gonzales(2), K. Raatikainen(3), U. Sankilampi(4), S. Heinonen(3), P. Neuvonen (5), V-P. Ranta(1), H. Kokki(2)
(1) Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; (2) Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland; (3) Department of Obstetrics and Gynaecology, Kuopio University Hospital, Kuopio, Finland; (4) Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland; (5) Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland
Objectives: Oxycodone has been the most commonly used opiod in treatment of post-operative pain in Finland for the last 50 years. There have been no previous studies about the pharmacokinetics of oxycodone in labouring women. Based on case reports of neonatal oxycodone abstinence syndrome [1], it seems that oxycodone can permeate placenta. This study was set up to investigate the pharmacokinetics of oxycodone in labouring women and to preliminary quantify the neonatal exposure to oxycodone following maternal administration.
Methods: Fifteen women were included in the study. The participants were previously healthy and their pregnancies were normal. The women received an initial dose of 780 µg of free oxycodone base and the dose was repeated as necessary in five minute intervals (up to a maximum of 3.9 mg). Venous blood samples were taken 5 minutes after each oxycodone administration, at 10, 30, 60 minutes after the last oxycodone dose, and after that at every 60 minutes until birth. The umbilical cord was clamped at delivery, and venous and arterial blood samples were drawn. The samples were analyzed with a highly sensitive LC-MS/MS method [2].
A total of 171 venous plasma samples from mothers, 15 arterial and 14 venous umbilical cord samples were above limit of quantitation. The pharmacokinetics of oxycodone in mother was characterized by a two-compartment model. In addition, umbilical vena, the neonate, and umbilical artery were implemented as separate compartments.
Results: The clearance of oxycodone was 0.84 L/min/(70kg)0.75. The central and peripheral volumes of distribution were 79 and 88 L/70kg, respectively. The inter-compartmental clearance was 2.9 L/min /(70kg)0.75. The transfer rate from mother to neonate was similar to the transfer rate from neonate to mother. The residual error was 12% for venous mother concentrations and 32% for umbilical cord concentrations. All fixed-effects parameters were fairly well estimated (RSE < 25%).
Conclusions: The pharmacokinetics of oxycodone in labouring women was similar to that in healthy volunteers [3]. Oxycodone permeates the placenta and distributes into the neonate. Since the number of subjects in this study was small, these results should be considered preliminary.
References:
[1] 1. Rao R, Desai NS. OxyContin and neonatal abstinence syndrome. J Perinatol. 2002;22(4):324-5.
[2] 2. Neuvonen M, Neuvonen PJ. Determination of oxycodone, noroxycodone, oxymorphone, and noroxymorphone in human plasma by liquid chromatography-electrospray-tandem mass spectrometry. Ther Drug Monit. 2008;30(3):333-40.
[3]3. R Pöyhiä, K T Olkkola, T Seppälä, and E Kalso. The pharmacokinetics of oxycodone after intravenous injection in adults. Br J Clin Pharmacol. 1991; 32(4): 516518.
