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A pharmacogenetic study of uridine diphosphate–glucuronosyltransferase 2B7 in patients receiving morphine
Author(s) -
Sawyer Michael B.,
Innocenti Federico,
Das Soma,
Cheng Cheng,
Ramírez Jacqueline,
PantleFisher Friedl H.,
Wright Constance,
Badner Judith,
Pei Deqing,
Boyett James M.,
Cook Edwin,
Ratain Mark J.
Publication year - 2003
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(03)00053-5
Subject(s) - ugt2b7 , glucuronidation , morphine , uridine , chemistry , uridine diphosphate , glucuronide , glucuronosyltransferase , linkage disequilibrium , pharmacokinetics , pharmacogenetics , pharmacology , medicine , genotype , endocrinology , biochemistry , in vitro , metabolism , single nucleotide polymorphism , gene , microsome , enzyme , rna
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. Clinical Pharmacology & Therapeutics (2003) 73 , 566–574; doi: 10.1016/S0009‐9236(03)00053‐5