2003 Fiscal Year Final Research Report Summary
Effect of genetic polymorphism of UGT2B7 on pharmacokinetics of morphine in cancer patients
| Project/Area Number |
14572155
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
OHASHI Kyoichi Hamamatsu University, School of Medicine, Clinical Pharmacology and therapeutics, Professor, 医学部, 教授 (20137714)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Hisakuni Hamamatsu University, School of Medicine, Pharmacy, Professor, 医学部附属病院, 教授 (10009558)
UCHIDA Shinya Hamamatsu University, School of Medicine, Clinical Pharmacology and therapeutics, Assistant Professor, 医学部, 助手 (80372522)
KOSUGE Kazuhito Hamamatsu University, School of Medicine, Clinical Pharmacology and therapeutics, Assistant Professor (00283375)
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| Project Period (FY) |
2002 – 2003
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| Keywords | morphine / UGT2B7 / genetic polymorphism |
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| Research Abstract |
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.
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