Population Pharmacokinetic-Pharmacodynamic Study of Intravenous Oxycodone in Children
Keywords
Abstract
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 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.
Dates
| Last Verified: | 03/31/2019 |
| First Submitted: | 03/24/2016 |
| Estimated Enrollment Submitted: | 03/29/2016 |
| First Posted: | 04/04/2016 |
| Last Update Submitted: | 04/17/2019 |
| Last Update Posted: | 04/21/2019 |
| Actual Study Start Date: | 03/31/2016 |
| Estimated Primary Completion Date: | 03/31/2019 |
| Estimated Study Completion Date: | 11/30/2019 |
Condition or disease
Intervention/treatment
Drug: Active
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Other: Active Open label IV Oxycodone 0.1 mg/kg Bolus Pharmacokinetic-Pharmacodynamic Study | Drug: Active Pain Management |
Eligibility Criteria
| Ages Eligible for Study | 3 Years To 3 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - Aged between 3 to 17 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. |
Outcome
Primary Outcome Measures
1. Clearance (CL) [18 months]
Secondary Outcome Measures
1. Volume of distribution of IV oxycodone [18 months]
