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Population Pharmacokinetics and Dosing Simulations of Intravenous Oxycodone for Perioperative Pain Relief in Adult Surgical Patients with Obesity

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Abstract

Background and Objective

Oxycodone, a semisynthetic thebaine derivative µ-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/m2 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.

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Acknowledgements

The authors are grateful to the staff involved in the study. Mr. Mohd Shafiq for helping in the storage of plasma samples.

Author information

Authors and Affiliations

  1. Department of Anaesthesiology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia

    Sook Hui Chaw & Ina Ismiarti Shariffuddin

  2. Department of Pharmacy Practice, School of Pharmacy, International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia

    Yoke Lin Lo

  3. Universiti Malaya Specialist Centre, Lembah Pantai, 50603, Kuala Lumpur, Malaysia

    Li Ling Yeap

  4. School of Pharmacy, Monash University Malaysia, 47500 Subang Jaya, Selangor, Malaysia

    Li Ling Yeap

  5. The Institute of Research Management and Services, Deputy Vice-Chancellor (Research and Innovation), Universiti Malaya, 50603, Kuala Lumpur, Malaysia

    Didi Erwandi Bin Mohamad Haron

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  1. Sook Hui Chaw
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Corresponding author

Correspondence to Yoke Lin Lo.

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Author contributions

All authors contributed to the study's conception and design. Material preparation, data collection, and analysis were performed by Sook Hui Chaw and Yoke Lin Lo. The first draft of the manuscript was written by Sook Hui Chaw and all authors commented on the manuscript. The final version of the manuscript was read and approved by all authors.

Funding

This study received funding from Institut Pengurusan dan Pemantauan Penyelidikan, Universiti Malaya, Bantuan Kecil Penyelidikan (BKP) BK031-2016.

Conflict of interest

Sook Hui Chaw, Yoke Lin Lo, Li Ling Yeap, Didi Erwandi Bin Mohamad Haron, and Ina Ismiarti Shariffuddin declare that they have no conflicts of interest.

Availability of data and materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

The model code can be obtained from the corresponding author on reasonable request.

Ethics approval

This study was performed in line with the principles of the 1964 Declaration of Helsinki and its later amendments. Approval was granted by the UMMC Medical Ethics and Research Committee (MERC number: 20162-2143).

Consent to participate

Informed consent was obtained from all participants included in the study.

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Chaw, S.H., Lo, Y.L., Yeap, L.L. et al. Population Pharmacokinetics and Dosing Simulations of Intravenous Oxycodone for Perioperative Pain Relief in Adult Surgical Patients with Obesity. Eur J Drug Metab Pharmacokinet 48, 11–21 (2023). https://doi.org/10.1007/s13318-022-00795-4

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  • DOI: https://doi.org/10.1007/s13318-022-00795-4

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