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

Clin Pharmacol Ther. 2006 Apr;79(4):316-24. doi: 10.1016/j.clpt.2006.01.007.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Adult
  • Aged
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Colorectal Surgery
  • Female
  • Glucuronosyltransferase / drug effects
  • Glucuronosyltransferase / genetics
  • Humans
  • Male
  • Middle Aged
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Pain Measurement
  • Pain, Postoperative / pathology
  • Pain, Postoperative / prevention & control
  • Pilot Projects
  • Polymorphism, Single Nucleotide
  • Postoperative Nausea and Vomiting / pathology
  • Postoperative Nausea and Vomiting / prevention & control
  • Postoperative Period
  • Receptors, Opioid, mu / drug effects*
  • Receptors, Opioid, mu / genetics

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Analgesics, Opioid
  • OPRM1 protein, human
  • Receptors, Opioid, mu
  • Morphine
  • UGT2B7 protein, human
  • Glucuronosyltransferase