Population Pharmacokinetics and Pharmacogenomics of Oral Oxycodone in Pediatric Surgical Patients
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|ClinicalTrials.gov Identifier: NCT02044497|
Recruitment Status : Recruiting
First Posted : January 24, 2014
Last Update Posted : August 22, 2017
|Condition or disease||Intervention/treatment||Phase|
|Pediatric Surgical Patient||Drug: oral oxycodone||Phase 4|
Oxycodone is the most commonly used analgesic for the management of moderate and severe postoperative pain. The efficacy of Oxycodone as a potent opioid has been confirmed in children.
The principal metabolic pathway of oxycodone in humans is N-demethylation via enzyme CYP3A4 to generate inactive noroxycodone.  A smaller amount (approximately 11%) is O-demethylated by cytochrome P450 enzyme CYP2D6 to become oxymorphone, the active and potent metabolite which exhibits about 40 times the affinity and 8 times the potency on μ-opioid receptors compared to the mother substance. Approximate frequencies of cytochrome P450 enzyme CYP2D6 phenotypes for the Caucasian population are: poor metabolizers 5 - 10%, extensive/intermediate metabolizers 65-90%, and ultra-rapid metabolizers 5 - 10%. Kirchheiner and colleagues noticed more codeine-related sedative side-effects in ultra-rapid metabolizers. In studies investigating extensive and poor metabolizers, codeine side-effects do not seem to be related to CYP2D6 genotype. However, clinical investigations of CYP2D6 genotype in the postoperative pain setting have shown conflicting results, and well-designed prospective studies are lacking. Taken together, these results demonstrate the need for careful pharmacokinetic studies in children who received a pharmacologic agent, such as oxycodone, which is metabolized by the enzyme CYP2D6.
The population PK of oxycodone and its metabolites has not been fully established for oral oxycodone in pediatric patients. In addition, there is a group of ultra-rapid metabolizers (approximately 4.5% of the population, but as high as 20% in some particular ethnic groups; East African and Saudi Arabian populations) which may be at risk for serious side effects in the commonly prescribed dose (which is extrapolated from adult recommendations). Given that BCH has switched (from codeine) to oxycodone as the most common opioid prescribed for all postoperative patients and the recent concerns of serious side effects from codeine. It is important to further investigate oral oxycodone to optimize dosing recommendations.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||68 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Population Pharmacokinetics and Pharmacogenomics of Oral Oxycodone in Pediatric Surgical Patients|
|Study Start Date :||May 2014|
|Estimated Primary Completion Date :||June 2018|
|Estimated Study Completion Date :||December 2018|
Experimental: oral oxycodone
An orogastric tube will be placed in the stomach (placement verified by routine accepted clinical guidelines) under anesthesia as is part of standard routine clinical care to remove gastric contents. The same orogastric tube will be used for intragastric liquid oxycodone administration in a dose of 0.1 mg/kg before the surgical incision. This weight-adjusted dose of 0.1 mg/kg is administered as per standard clinical dosing guidelines at Boston Children's Hospital.
Drug: oral oxycodone
- Oxycodone, oxymorphone, noroxymorphone and noroxycodone serum levels [ Time Frame: The 10 samples will be drawn at the following time points: 8 blood samples will be taken at 30 minutes, 1, 1.5, 2, 3, 4, 5, and 6 hours post-dose in every patient along other 2 samples at approximately either 8 and 12 or 10 and 24 hours post-dose. ]Oxycodone, oxymorphone, noroxymorphone and noroxycodone levels, at 10 time points, will be used to determine the single-dose Pharmacokinetics (PK) metric.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02044497
|Contact: Christine Dube, MS, BSN, RN||617-355-6185||Christine.Dube@childrens.harvard.edu|
|Contact: Rachel Bernier, BS, MPH||857-218-5348||Rachel.Bernier@childrens.harvard.edu|
|United States, Massachusetts|
|Boston Children Hospital||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Christine Dube, MS, BSN, RN 617-355-6185 Christine.Dube@childrens.harvard.edu|
|Principal Investigator: Patcharee Sriswasdi, MD|
|Principal Investigator:||Patcharee Sriswasdi, MD||Boston Children Hospital|