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The hypoalgesic effect of oxycodone in human experimental pain models in relation to the CYP2D6 oxidation polymorphism.

Abstract：

:Oxycodone is O-demethylated by CYP2D6 to oxymorphone which is a potent micro-receptor agonist. The CYP2D6 oxidation polymorphism divides the Caucasian population in two phenotypes: approximately 8% with no enzyme activity, poor metabolizers (PM) and the remainder with preserved CYP2D6 activity, extensive metabolizers (EM). The objective of the study was to determine if the analgesic effect of oxycodone in human experimental pain depends on its metabolism to oxymorphone. The analgesic effect of oxycodone was evaluated in a randomized, placebo-controlled, double-blinded, crossover experiment including 33 (16 EM and 17 PM) healthy volunteers. Pain tests were performed before and 1, 2, 3 and 4 hr after medication and included pain detection and tolerance thresholds to single electrical sural nerve stimulation, pain summation threshold to repetitive electrical sural nerve stimulation and the cold pressor test with rating of discomfort and pain-time area under curve (AUC(0-2 min.)). For single sural nerve stimulation, there was a less pronounced increase in thresholds on oxycodone in pain detection (9% vs. 20%, P = 0.02, a difference of 11%, CI: 2%-20%) and pain tolerance thresholds (15% vs. 26%, P = 0.037, a difference of 10%, CI: 1%-20%) for PM compared with EM. In the cold pressor test, there was less reduction in pain AUC on oxycodone for PM compared with EM (14% vs. 26%, P = 0.012, a difference of 12%, CI: 3%-22%). The plasma oxymorphone/oxycodone ratio was significantly lower in PM compared with EM (P < 0.001). Oxycodone analgesia seems to depend both on oxycodone itself and its metabolite oxymorphone.

journal_name

Basic Clin Pharmacol Toxicol

journal_title

Basic & clinical pharmacology & toxicology

authors

Zwisler ST,Enggaard TP,Noehr-Jensen L,Pedersen RS,Mikkelsen S,Nielsen F,Brosen K,Sindrup SH

doi

10.1111/j.1742-7843.2009.00378.x

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

335-44

issue

4

eissn

1742-7835

issn

1742-7843

pii

PTO378

journal_volume

104

pub_type

杂志文章,随机对照试验

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