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Clin Pharmacol Ther. 2006 Apr;79(4):316-24.

Environmental and genetic factors associated with morphine response in the postoperative period.

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  • 1Pharmacology Department, Saint Antoine University of Medicine, University Pierre et Marie Curie, Paris, France.

Abstract

OBJECTIVE:

The aim of this study was to investigate the respective influence of genetic and nongenetic factors on morphine dose requirements and adverse effects after colorectal surgery.

METHODS:

Seventy-four patients who planned to undergo colorectal surgery were included in this pilot study. The cumulative 24-hour postoperative dose of morphine and postoperative nausea or vomiting requiring the antiemetic ondansetron were the 2 clinical end points. The association of patient characteristics, A118G mu-opioid receptor (OPRM1) single-nucleotide polymorphism (SNP); T802C uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7) SNP; and 2 adenosine triphosphate-binding cassette, subfamily B, member 1 (ABCB1) (multidrug resistance 1 [MDR1]) exonic SNPs (G2677T/A and C3435T) with study end points was investigated.

RESULTS:

Age, creatinine clearance, and the regular use of psychotropic agents were found to be significantly associated with postoperative morphine dose requirements by univariate analysis. Multivariate analysis identified that age (P = .01) and the use of psychotropic agents before surgery (P = .03) were positively associated with a higher rate of morphine consumption. A higher weight (P = .05) and the ABCB1 homozygous GG-CC diplotype (P = .03) were significantly associated with fewer morphine side effects by univariate analysis. The homozygous ABCB1 diplotype (GG-CC) conferred an odds ratio of 0.12 (95% confidence interval, 0.01-0.98) with regard to the use of ondansetron for postoperative nausea or vomiting. Multivariate analysis identified that the ABCB1 GG-CC diplotype was the only borderline-significant (P = .07) predictive factor of morphine side effects.

CONCLUSION:

Age and prior use of psychotropic agents are associated with postoperative morphine dose requirements. Whether ABCB1 polymorphisms might predict morphine side effects remains to be determined.

PMID:
16580900
DOI:
10.1016/j.clpt.2006.01.007
[PubMed - indexed for MEDLINE]
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