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. Clinical Pharmacology & Therapeutics (2003) 73, 566–574; doi: 10.1016/S0009‐9236(03)00053‐5