OXY-2: The Pharmacogenetics of Oxycodone Analgesia in Human Experimental Pain Models
OXY-2: The Pharmacogenetics of Oxycodone Analgesia in Human Experimental Pain Models
Thirty-two healthy volunteers will be submitted to experimental pain and on the 2 study days
 receive Oxycodone 20 mg po vs. placebo. Half of the volunteers will be poor metabolizers
 according to CYP2D6 genotype and half will be extensive metabolizers (EM) and have an enzyme
 with normal function. The study hypothesis is that PM will experience less pain relief than
 EM.
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.

 Electrical stimulation and cold pressor test are among the most well defined and evaluated
 human experimental pain models. The 32 volunteers will be submitted to the tests before and
 1, 2, 3 and 4 hours after medicine intake.

 To determine the plasma levels of Oxycodone and its metabolites blood will be drawn after
 each pain test. Also the CYP2D6 genotype and the above mentioned SNPs will be determined from
 the blood samples.
Inclusion Criteria:

 -  Healthy volunteer age between 20 and 40 years.

 -  Healthy according to medical history and physical examination.

 -  Informed consent given.

 -  Phenotyped or genotyped as extensive or poor metabolizer of sparteine.

 -  Female: Use of safe contraception (IUD, gestagen injectiones or oral contraceptive) or
 negative u-HCG test.

 Exclusion Criteria:

 -  Any known allergy or intolerance to oxycodone.

 -  Regularly drug therapy or medication (except contraceptives).

 -  Alcohol or medicine abuse.