Effect of genetic polymorphism of UGT2B7 on pharmacokinetics of morphine in cancer patients

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Morphine is metabolized through glucuronide conjugation by the enzyme, UGT2B7 into morphine-3-glucuronic acid (M-3-G) and morphine-6-glucuronic acid (M-6-G). The plasma M-3-G/M ratio has been thought to be an index of morphine metabolic activity in the liver. There is a missense variant of UGT2B7 at 802C/T in exon 2. This study investigated whether genetic variants of UGT2B7 are associated with the inter-individual variability in morphine metabolism in patients with cancer pain. The M-3-G/M ratio of the oral morphine administration was higher than that of the continuous morphine infusion(p<0.001). The M-3-G/M ratio showed inter-individual variations of about 10 fold between the minimum and the maximum value, regardless of the route of administration for morphine. In this patient group, no variant of 802C/T in exon2, nor TATA-box at core promoter region were found. However, a new SNP, T replaced A, at position-125 was found in 17.4% of cancer patients who showed the tendency of the low glucuronidators. This study suggests that the variability in the metabolism of morphine may be related to genetic polymorphism of UGT2B7.