A Pharmacogenetic Study of Uridine Diphosphate-Glucuronosyltransferase 2B7 in Patients Receiving Morphine

Clin Pharmacol Ther. 2003 Jun;73(6):566-74. doi: 10.1016/S0009-9236(03)00053-5.

Abstract

We investigated the variation in the uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7) gene in patients receiving patient-controlled analgesia with morphine. UGT2B7 was sequenced in phenotypic extremes (n = 12) of the distribution of morphine-6-glucuronide/morphine plasma ratios. A new -161C/T promoter variant was in complete linkage disequilibrium with the 802C/T variant and was more frequent in low glucuronidators (P =.039). Both variants were genotyped in all patients (n = 86), and complete linkage disequilibrium was confirmed. Trend analysis showed reduced morphine-6-glucuronide/morphine ratios in patients with T/T, C/T, and C/C genotypes (T/T > C/T > C/C) (P =.031). Morphine levels were lower in T/T patients (median, 18 ng/mL [range, 18-1490 ng/mL]) as compared with C/T and C/C patients combined (median, 66 ng/m; range, 18-3995 ng/mL) (P =.04). Morphine-6-glucuronide and morphine-3-glucuronide concentrations were significantly lower in C/C patients (median, 18 ng/mL; range, 0-66 ng/mL; and median, 152 ng/mL; range, 30-434 ng/mL; respectively) compared with C/T and T/T patients combined (median, 43 ng/mL; range, 0-193 ng/mL; and median, 242 ng/mL; range, 33-1381 ng/mL; respectively) (P =.045 and P =.004, respectively). Interindividual differences in morphine glucuronidation may be the result of genetic variation in UGT2B7, and further studies are indicated.

Publication types

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

MeSH terms

  • Adult
  • African Continental Ancestry Group
  • Aged
  • Aged, 80 and over
  • Analgesia, Patient-Controlled
  • Analgesics, Opioid / pharmacokinetics
  • Analgesics, Opioid / pharmacology*
  • Biotransformation
  • European Continental Ancestry Group
  • Female
  • Genotype
  • Glucuronosyltransferase / biosynthesis
  • Glucuronosyltransferase / genetics*
  • Humans
  • Indicators and Reagents
  • Male
  • Middle Aged
  • Morphine / pharmacokinetics
  • Morphine / pharmacology*
  • Morphine Derivatives / blood
  • Phenotype

Substances

  • Analgesics, Opioid
  • Indicators and Reagents
  • Morphine Derivatives
  • morphine-6-glucuronide
  • Morphine
  • UGT2B7 protein, human
  • Glucuronosyltransferase
  • morphine-3-glucuronide