A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine.
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.
Sawyer
Michael B
MB
Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, IL, USA.
Innocenti
Federico
F
Das
Soma
S
Cheng
Cheng
C
Ramírez
Jacqueline
J
Pantle-Fisher
Friedl H
FH
Wright
Constance
C
Badner
Judith
J
Pei
Deqing
D
Boyett
James M
JM
Cook
Edwin
E
Ratain
Mark J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology*; D001711:Biotransformation; D044383:Black People; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000493:pharmacokinetics / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000097:blood; D010641:Phenotype; D044465:White People
D000701:Analgesics, Opioid; D007202:Indicators and Reagents; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; C018108:morphine-3-glucuronide