Population Pharmacokinetic-Pharmacodynamic Study of Intravenous Oxycodone in Malaysian Population

Pain Clinical Trial

Official title:

Population Pharmacokinetic-Pharmacodynamic Study of Intravenous Oxycodone in Malaysian Population

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02728648
• Other study ID #: 20162-2143
• Status: Completed
• Phase: Phase 4
• Start date: April 2016
• Est. completion date: November 2017

Study information

• Verified date: January 2022
• Source: University of Malaya
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: November 2017
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 65 Years

Eligibility

Inclusion Criteria:

• Aged between 3 to 65 years

• Generally healthy as documented by medical history (ASA 1-II)

• Opioid-naïve

• Patient is scheduled for a surgical procedure/procedures that is/are expected to require an analgesia with an opiate level medication.

• Patient who will remain hospitalized for at least 24 hours after dosing with the study drug.

• A negative urine pregnancy test at screening for females of childbearing potential

Exclusion Criteria:

• Patient is a lactating or breastfeeding female

• Patient has known allergy to oxycodone or any ingredient in oxycodone dosage form.

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• Oxycodone
Pain Management

Locations

Country	Name	City	State
Malaysia	Faculty of Medicine, University of Malaya	Kuala Lumpur	Wilayah Persekutuan

Sponsors (1)

Lead Sponsor	Collaborator
University of Malaya

Country where clinical trial is conducted

Malaysia, 

References & Publications (4)

Kalso E, Pöyhiä R, Onnela P, Linko K, Tigerstedt I, Tammisto T. Intravenous morphine and oxycodone for pain after abdominal surgery. Acta Anaesthesiol Scand. 1991 Oct;35(7):642-6. — View Citation

Kokubun H, Yoshimoto T, Hojo M, Fukumura K, Matoba M. Pharmacokinetics of oxycodone after intravenous and subcutaneous administration in Japanese patients with cancer pain. J Pain Palliat Care Pharmacother. 2014 Dec;28(4):338-50. doi: 10.3109/15360288.2014.969872. Epub 2014 Oct 31. — View Citation

Olkkola KT, Hamunen K, Seppälä T, Maunuksela EL. Pharmacokinetics and ventilatory effects of intravenous oxycodone in postoperative children. Br J Clin Pharmacol. 1994 Jul;38(1):71-6. — View Citation

Pöyhiä R, Olkkola KT, Seppälä T, Kalso E. The pharmacokinetics of oxycodone after intravenous injection in adults. Br J Clin Pharmacol. 1991 Oct;32(4):516-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clearance (CL)	Clearance: volume of plasma from which oxycodone is completely removed per unit time;	18 months
Secondary	Volume of distribution of IV oxycodone	Volume of distribution: theoretical volume that would be necessary to contain the total amount of oxycodone at the same concentration that it is observed in the blood plasma.	18 months