Impact of the CYP2D6 genotype on post-operative intravenous oxycodone analgesia.
BACKGROUND
Oxycodone is a semi-synthetic opioid with a mu-receptor agonist-mediated effect in several pain conditions, including post-operative pain. Oxycodone is metabolized to its active metabolite oxymorphone by O-demethylation via the polymorphic CYP2D6. The aim of this study was to investigate whether CYP2D6 poor metabolizers (PMs) yield the same analgesia post-operatively from intravenous oxycodone as extensive metabolizers (EMs).


METHODS
Two hundred and seventy patients undergoing primarily thyroid surgery or hysterectomy were included and followed for 24 h post-operatively. The CYP2D6 genotype was blinded until study procedures had been completed for all patients. All patients received intravenous oxycodone as pain treatment for 24 h post-operatively and morphine 5 mg was used as escape medication. A responder was characterized as a patient without the need for escape medication and a positive evaluation in a questionnaire 24 h post-operatively.


RESULTS
Twenty-four patients were PM (8.9%) and 246 were EM (91.1%). One PM (4.17%, CI=0.1-21.1) was a non-responder and 42 EM (17.07%, CI=12.6-22.4) were non-responders. The non-responder rate did not differ between the two genotypes (P=0.14). There was no difference in the total consumption of oxycodone between the two genotypes (EM=14.7 mg, CI=13.0-16.4 and PM=13.0 mg, CI=8.9-17.0, P=0.42). The mean oxymorphone/oxycodone ratios were 0.0031 and 0.00081 in the EMs and PMs, respectively (P<0.0001).


CONCLUSIONS
This study showed for the first time in patients that the oxymorphone formation depends on CYP2D6, but we found no difference in the post-operative analgesic effect of intravenous oxycodone between the two CYP2D6 genotypes.
Zwisler
S T
ST
Department of Anaesthesiology and Intensive Care, Odense University Hospital, Odense, Denmark. stinezwisler@hotmail.com
Enggaard
T P
TP
Mikkelsen
S
S
Brosen
K
K
Sindrup
S H
SH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D000932:Antiemetics / Q000627:therapeutic use; D003243:Consciousness / Q000187:drug effects; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007275:Injections, Intravenous; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D010111:Oxymorphone / Q000097:blood; D010147:Pain Measurement; D010149:Postoperative Pain / Q000517:prevention & control*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D000932:Antiemetics; D009466:Neuromuscular Blocking Agents; D009020:Morphine; D010111:Oxymorphone; D010098:Oxycodone; D019389:Cytochrome P-450 CYP2D6