OXY-1: The Pharmacogenetics of Oxycodone Analgesia in Postoperative Pain
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed 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.
    

Intervention name(s): Oxycodone
Intervention type(s): Drug
Intervention MeSH terms: Oxycodone
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment