OXY-1: The Pharmacogenetics of Oxycodone Analgesia in Postoperative Pain

Odense University Hospital

Status and phase

Completed

Phase 4

Conditions

Postoperative Pain

Treatments

Drug: Oxycodone

Study type

Interventional

Funder types

Other

Identifiers

NCT00260260

EudraCT 2005-001145-42

Details and patient eligibility

About

Patients undergoing surgery (thyroidectomy and hysterectomy) will postoperatively receive oxycodone intravenously (IV) as pain management with morphine as an escape medicine, if there is insufficient pain relief with oxycodone. Patients' pain and side effects will be registered and after 24 hours they will answer a questionnaire. All included patients will be genotyped accordingly to CYP2D6 and relevant single nucleotide polymorphisms (SNPs), and measures of plasma levels of oxycodone will be performed.

Full description

Oxycodone is a semi-synthetic opioid with an analgesic effect in the postoperative pain management comparable to morphine. Oxycodone is N-demethylated by CYP2D6 to its active metabolite oxymorphone, a potent μ-receptor agonist. A genetic polymorphism divides a Caucasian population into two groups: 8% with an enzyme lacking activity, poor metabolizers (PM) and the rest with normal CYP2D6 activity, extensive metabolizers (EM).

Many different, single nucleotide polymorphisms (SNPs) are responsible for interindividual differences in the effect of opioids. Among these are the A118G SNP in the μ-receptor gene OPRM1 and the C3435T and G2677T/A SNPs in the MDR-1 gene of P-glycoprotein. P-glycoprotein is responsible for the absorption, excretion and transport of many drugs including opioids over the blood-brain barrier.

The patients will receive the first Oxycodone dosis of 5 mg iv at the end of the surgery. If their pain is not sufficiently relieved they can be given maximum two times Oxycodone 5 mg iv in the recovery room. If still not sufficiently pain relieved they will be given escape medication (Morphine 5 mg iv) until sufficient pain relief.

Further pain treatment will be by Patient Controlled Analgesia (PCA) with bolus doses of Oxycodone 2 mg iv.

During the first 24 hours postoperatively the patients pain and side effects will be registered.

Three blood samples will be drawn: 1. approximately 30 minutes after first Oxycodone dosis, 2. before leaving the recovery room a couple of hours after surgery and 3. 24 hours after surgery. From these samples plasma levels of Oxycodone and its metabolites will be determined and the genotype of CYP2D6 and the above mentioned SNPs will be determined.

The patients will be divided into two groups: Responder and Non-responder. The Responders are characterized by no use of escape medication (morphine) and satisfaction with pain management in final questionnaire. The Non-responders are characterized by use of escape medicine and/or dissatisfaction with pain management in final questionnaire.

Enrollment

300 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Ages 18-80 years old
Caucasian race
Signed informed consent
Patients admitted for one of the following operations: thyroidectomy, mastectomy, hysterectomy, mammaexpander operation, nasal septum correction and jaw operations.

Exclusion criteria

Allergy towards oxycodone
Previous daily opioid use
Known severe illness (terminal cancer, severe dementia, uncompensated heart failure, kidney failure, liver failure and severe lung failure)
Lack of ability to use patient controlled analgesia or to follow the trial protocol
Pregnancy
Severe psychiatric illness
Alcoholism
Ongoing treatment with potent CYP2D6 inhibitors (fluoxetine, paroxetine and terbinafine)
Severe perioperative complications or re-operation within the first 24 hours
Use of extra pain management during the anaesthesia with an effect after the operation