Chaw, Sook Hui and Lo, Yoke Lin and Yeap, Li Ling and Mohamad Haron, Didi Erwandi and Shariffuddin, Ina Ismiarti (2023) Population pharmacokinetics and dosing simulations of intravenous oxycodone for perioperative pain relief in adult surgical patients with obesity. European Journal of Drug Metabolism and Pharmacokinetics, 48 (1). pp. 11-21. ISSN 0378-7966, DOI https://doi.org/10.1007/s13318-022-00795-4.
Full text not available from this repository.Abstract
Background and Objective Oxycodone, a semisynthetic thebaine derivative mu-opioid (MOP) receptor agonist, is effective for treating moderate and severe pain in different clinical conditions. The pharmacokinetics of intravenous oxycodone in the obese population has not been studied. This study aims to characterize the pharmacokinetic profile of oxycodone after intravenous administration and to simulate an appropriate dosage for analgesic efficacy in obese patients. Methods We recruited 33 (age range from 21 to 72 years) adult patients with a body mass index of 30 kg/m(2) and above, who were scheduled for non-cardiac surgeries. Intravenous oxycodone was administered after induction of general anesthesia and blood samples were collected up to 24 h after oxycodone administration. Plasma concentrations of oxycodone were assayed using liquid chromatography-tandem mass spectrometry and 253 concentration-time points were used for pharmacokinetic analysis using nonlinear mixed-effects modeling. Results Intravenous oxycodone pharmacokinetics were well described by a two-compartment open model. The estimated total clearance and central volume of distribution of oxycodone are 28.5 l/h per 70 kg and 56.4 l per 70 kg, respectively. Total body weight was identified as a significant covariate of the clearance and central volume of distribution. Dosing simulations based on the final model demonstrate that a starting dose of 0.10 mg/kg of intravenous oxycodone is adequate to achieve a target plasma concentration and repeated doses of 0.02 mg/kg may be administered at 1.5-h intervals to maintain a plasma concentration within an effective analgesic range. Conclusions A population pharmacokinetic model using total body weight as a covariate supports the administration of 0.10 mg/kg of intravenous oxycodone as a starting dose and repeated doses of 0.02 mg/kg at 1.5-h intervals to maintain targeted plasma concentrations for analgesia in the obese adult population.
| Item Type: | Article |
|---|---|
| Funders: | Institut Pengurusan dan Pemantauan Penyelidikan, Universiti Malaya, Bantuan Kecil Penyelidikan (BKP) (Grant No: BK031-2016) |
| Uncontrolled Keywords: | Plasma-concentrations; Opioid analgesics; Oral oxycodone; Metabolism; Liver; Elimination; Morphine; Model; Age |
| Subjects: | R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Medicine > Anaesthesiology Department Deputy Vice Chancellor (Research & Innovation) Office > Institute of Research Management and Services |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 27 Nov 2023 04:39 |
| Last Modified: | 27 Nov 2023 04:39 |
| URI: | http://eprints.um.edu.my/id/eprint/39408 |
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