Population Pharmacokinetic-Pharmacodynamic Study of Intravenous Oxycodone in Malaysian Population

Overview

Oxycodone has been in clinical use for decades. It is an effective alternative to morphine for moderate to severe acute or chronic pain and has been found to improve quality of life. The drug has been used parenterally or orally as perioperative analgesia or for cancer pain relief. Despite its long clinical experience, prescribing errors and misuse may lead to addiction and accidental overdose. Currently, little is known about the pharmacokinetic properties of intravenous oxycodone among paediatric patients in this region even though the drug has been used in children in other countries such as Finland. Therefore, a pharmacokinetic-pharmacodynamic study of oxycodone among Malaysian pediatric patients is warranted.

Oxycodone (14-hydroxy-7,8 dihydrocodeinone) is a strong, semisynthetic thebaine derivative µ-opioid receptor agonist. This drug is an effective alternative to morphine for moderate-to-severe pain. Oxycodone has been used parenterally or orally for perioperative analgesia or for cancer pain relief. The drug has a longer analgesic action than morphine. In terms of analgesic potency, intravenous oxycodone is about 1.6 times The adverse effects of oxycodone are mostly similar to those of other opioids. Oxycodone, however, does not cause histamine release. The drug induces less nausea and vomiting, less sedating, and less central nervous system excitatory effects than morphine. A large between-subject variability in pharmacokinetic properties of oxycodone has been observed. The variability could be attributed to the different body size and age-related difference in drug elimination organ system function. A 2-compartment first-order open model describes oxycodone pharmacokinetics in Finnish children (age 5.4±2.1 years) after an intravenous bolus dose of 0.1 mg kg-1 for post ophthalmic surgery pain relief. The authors reported a mean clearance (CL) and the steady-state volume of distribution (Vss) of oxycodone 15.2 mL min-1 kg-1 (0.912 L h-1 kg-1) and 2.1 L kg-1 respectively. A greater ventilator depression than comparable analgesic doses of other opioids was also observed. A pharmacokinetic study carried out in 9 young Finnish adult surgical patients reveals a clearance of 0.78 L min-1 (46.8 L h-1) and a volume of distribution (V) of 2.60 L kg-1. The mean area under the curve (AUC)( t=0,12) ratio of noroxycodone (main metabolite) to oxycodone is 0.33. In a study on 69 Japanese adults (mean age 66 years, mean weight 52.8 kg) receiving intravenous oxycodone for cancer pain relief, a one-compartment first-order open model describes the pharmacokinetics of oxycodone. The mean CL and volume of distribution (V) are 24.6 L h-1 and 214 L or 4.053 L kg-1.