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Rapid CommunicationAccelerated Communication

Human UGT2B7 Catalyzes Morphine Glucuronidation

Birgit L. Coffman, Gladys R. Rios, Christopher D. King and Thomas R. Tephly
Drug Metabolism and Disposition January 1997, 25 (1) 1-4;
Birgit L. Coffman
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Gladys R. Rios
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Christopher D. King
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Thomas R. Tephly
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Abstract

A human UDP-glucuronosyltransferase (UGT) catalyzing the glucuronidation of morphine has been identified. A full length cDNA was isolated from a human liver cDNA library and found to be identical to the UGT2B7 form having a tyrosine at position 268. This cDNA was transfected into HK 293 cells, and stable expression was achieved. Cell homogenates and membrane preparations from HK 293 cells expressing UGT2B7 catalyzed the glucuronidation of morphine and other clinically significant opioid agonists, antagonists, and partial agonists. UGT2B7 catalyzed morphine glucuronidation at the 3- and 6-hydroxy positions and also mediated the formation of codeine-6-glucuronide from codeine. This represents the first demonstration of a UGT capable of catalyzing the glucuronidation of both the 3- and 6-positions of opioids. Since humans excrete morphine-3-glucuronide and morphine-6-glucuronide after morphine administration, it is likely that UGT2B7 is a major isoform in humans responsible for the metabolism of this important drug and its surrogates.

Footnotes

  • Send reprint requests to: Dr. Thomas R. Tephly, 2-459 Bowen Science Building, Department of Pharmacology, University of Iowa, Iowa City, IA 52242.

  • This research was supported by the National Institutes of Health Grant GM26221.

  • ↵2 T. R. Tephly et al., unpublished data.

  • Abbreviations used are::
    UGT
    UDP-glucuronosyltransferase
    NSAID
    nonsteroidal anti-inflammatory drug
    UDP-GlcUA
    UDP-glucuronic acid
    SDS
    sodium dodecyl sulfate
    TBS
    10mM Tris, 0.9% NaCl, pH 7.4
    OH
    hydroxy
    • Received September 19, 1996.
    • Accepted October 28, 1996.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition
Vol. 25, Issue 1
1 Jan 1997
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Rapid CommunicationAccelerated Communication

Human UGT2B7 Catalyzes Morphine Glucuronidation

Birgit L. Coffman, Gladys R. Rios, Christopher D. King and Thomas R. Tephly
Drug Metabolism and Disposition January 1, 1997, 25 (1) 1-4;

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Rapid CommunicationAccelerated Communication

Human UGT2B7 Catalyzes Morphine Glucuronidation

Birgit L. Coffman, Gladys R. Rios, Christopher D. King and Thomas R. Tephly
Drug Metabolism and Disposition January 1, 1997, 25 (1) 1-4;
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