The antinociceptive effect and adverse drug reactions of oxycodone in human
experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes.
Author(s): Zwisler ST, Enggaard TP, Noehr-Jensen L, Mikkelsen S, Verstuyft C, Becquemont L,
Sindrup SH, Brosen K.
Affiliation(s): Clinical Pharmacology, Institute of Public Health, University of Southern
Denmark, Odense, Denmark. stinezwisler@hotmail.com
Publication date & source: 2010, Fundam Clin Pharmacol. , 24(4):517-24
The aim of this study was to search for a possible association between the
variant allele of the single nucleotide polymorphisms A118G in the OPRM1 gene and
C3435T and G2677T/A in the ABCB1 gene and altered antinociceptive effect and
adverse drug reactions of oxycodone. Thirty-three healthy subjects exposed to
experimental pain including electrical stimulation and the cold pressor test were
included. A118G: We found that the variant G allele was associated with reduced
antinociceptive effect as measured by pain tolerance thresholds to single
electrical nerve stimulation (8% increase vs. 25% for the wild-type carriers, P =
0.007). C3435T: The carriers of the variant T allele generally had less adverse
drug reactions on oxycodone than the carriers of the wild-type genotype.
G2677T/A: The carriers of the variant T allele had a better antinociceptive
effect of oxycodone than the carriers of the wild-type genotype in the cold
pressor test (25% reduction vs. 15%, P = 0.015 in the discomfort rating and 25%
reduction vs. 12%, P = 0.007 in the pain time AUC) and less adverse drug
reactions. The combined wild-type genotype 3435CC-2677GG was associated with less
antinociceptive effect of oxycodone in the discomfort rating of the cold pressor
test (13% reduction vs. 23%, P = 0.019) and more severe adverse drug reactions
than the carriers of the variant alleles. We found a moderate association between
less antinociceptive effect of oxycodone and the variant allele of A118G. There
was strong association between less adverse drug reactions of oxycodone and the
variant alleles of C3435T and G2677T/A.
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