Population pharmacokinetics and analgesic potency of oxycodone.

Abstract

This prospective study aimed to characterize the population pharmacokinetics of intravenous oxycodone and to determine the minimum effective concentration (MEC) and minimum effective analgesic concentration (MEAC) of oxycodone for major open intra-abdominal surgery. In the pharmacokinetic study, patients were administered intravenous oxycodone (0.1mgkg-1 ), and arterial blood was sampled at pre-set intervals. In the analgesic-potency study, patients were administered intravenous oxycodone (0.1mgkg-1 ) 30min before the end of the surgery, were placed in the postoperative anaesthesia care unit (PACU), and were asked to rate their pain every 10min using a visual analogue scale (0 = no pain, 10 = most severe pain). On the first occasion that wound pain at rest and during compression was rated as ≥3 or ≥5, respectively, the first blood sample was obtained to determine the MEC. A second blood sample was obtained after titration with 2mg of oxycodone to yield wound pain <3 at rest and <5 during wound compression, and MEAC was determined. MEC and MEAC were determined again in each patient. In the population pharmacokinetic study (n=54), oxycodone plasma concentration over time was well described by a three-compartment mammillary model. Lean body mass and age were significant covariates for the volume of distribution and metabolic clearance of the pharmacokinetic model of oxycodone, respectively. The analgesic-potency study (n=50) showed that the median (95% CI) MEC and MEAC were 31.5 (19.2-42.8) and 74.1 (29.2-128.3) ngml-1 (first measurements) and 63.4 (15.6-120.1) and 76.1 (32.9-132.7) ngml-1 (second measurements), respectively. In major intra-abdominal open surgery, the MEAC and analgesic potency of oxycodone were 75ngml-1 and 60ngml-1 , respectively.