3'-Azido-3'-deoxythimidine (AZT) is glucuronidated by human UDP- glucuronosyltransferase 2B7 (UGT2B7)

Drug Metabolism and Disposition

Volumn 28, Issue 5, 2000, Pages 497-502

  Barbier, Olivier ^b   Turgeon, David ^b   Girard, Caroline ^b   Green, Mitchell D ^a   Tephly, Thomas R ^a   Hum, Dean W ^b   Bélanger, Alain ^b  

^a UNIVERSITY OF IOWA   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

GLUCURONOSYLTRANSFERASE; ZIDOVUDINE;

ALLELISM; ARTICLE; DRUG CONJUGATION; DRUG GLUCURONIDATION; DRUG METABOLISM; ENZYME MECHANISM; ENZYME SPECIFICITY; HUMAN; HUMAN CELL; PRIORITY JOURNAL;

ALLELES; ANTI-HIV AGENTS; BLOTTING, WESTERN; CELL LINE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DNA; GLUCURONIDES; GLUCURONOSYLTRANSFERASE; HUMANS; ISOENZYMES; KINETICS; MASS SPECTROMETRY; MICROSOMES, LIVER; ZIDOVUDINE;

HUMAN IMMUNODEFICIENCY VIRUS;

EID: 0034007340     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (34)

1. Albert C, Vallée M, Beaudry G, Bélanger A and Hum DW (1999) The monkey and human uridine diphosphate-glucuronosyltransferase UGT1A9, expressed in steroid target tissues, are estrogen conjugating enzymes. Endocrinology 140:3292-3302.
2. Barry MG, Khoo SH, Veal GJ, Hoggard PG, Gibbons SE, Wilkins EG, Williams O, Breckenridge AM and Back DJ (1996) The effect of zidovudine dose on the formation of intracellular phosphorylated metabolites. AIDS 10:1361-1367.
3. 19 steroids. J Biol Chem 271:22855-22862.
4. Beaulieu M, Lévesque É, Hum DW and Bélanger A (1998) Isolation and characterization of a human orphan UDP-glucuronosyltransferase, UGT2B11. Biochem Biophys Res Commun 248:44-50.
5. Coffman BL, King CD, Rios GR and Tephly TR (1998) The glucuronidation of opioids, other xenobiotics, and androgens by human UGT2B7Y(268) and UGT2B7H(268) Drug Metab Dispos 26:73-77.
6. Crotty BK, Watson PV, Desmond ML, Mashford LJ, Wood J and Dudley FJ (1989) Hepatic extraction of morphine is impaired in cirrhosis. Eur J Clin Pharmacol 36:501-506.
7. Dutton GJ (1980) Glucuronidation of Drugs and Other Compounds, CRC Press, Boca Raton, FL.
8. Fischl MA, Richman DD, Grieco MH, Gottlieb MS, Volberding PA, Laskin OL, Leedom JM, Groopman JE, Mildvan D and Schooley RT (1987) The efficacy of azidothymidine (ZDV) in treatment of patients with AIDS and AIDS-related complex. N Engl J Med 317:185-191.
9. Fletcher CV and Balfour HH (1996) Variability in zidovudine serum concentration. Pharmacotherapy 16:1154-1158.
10. Good SS, Koble CS, Crouch R, Johnson RL, Rideout JL and de Miranda P (1990) Isolation and characterization of an either glucuronide of zidovudine, a major metabolite in monkeys and humans. Drug Metab Dispos 18:321-326.
11. Guillemette C, Lévesque É, Beaulieu M, Turgeon D, Hum WD and Bélanger A (1997) Differential regulation of two UDP-glucuronosyltransferases, UGT2B15 and UGT2B17, in human prostate LNCaP cells. Endocrinology 138:2998-3005.
12. Haumont M, Magdalou J, Lafaurie C, Ziegler JM, Siest G and Colin JN (1990) Phenobarbital inducible UDP-glucuronosyltransferase is responsible for glucuronidation of 3′-azido-3′-deoxythymidine: Characterization of the enzyme in human and rat liver microsomes. Arch Biochem Biophys 281:264-270.
13. Howe JL, Back DJ and Colbert J (1992) Extrahepatic metabolism of zidovudine. Br J Clin Pharmacol 33:190-192.
14. Hum DW, Bélanger A, Lévesque É, Barbier O, Beaulieu M, Albert C, Vallée M, Guillemette C, Tchernoff A, Turgeon D and Dubois S (1999) Characterization of UDP-glucuronosyltransferases active on steroid hormones. J Steroid Biochem Mol Biol 69:413-423.
15. Iyer L, King CD, Whitington PF, Green MD, Roy SK, Tephly TR, Coffman BL and Ratain MJ (1998) Genetic predisposition of the metabolism of Irinotecan (CPT-11). J Clin Invest 101:847-854.
16. Izuta S, Saneyoshi M, Sakurai T, Suzuki M, Kojima K and Yoshida S (1991) The 5′-triphosphate of 3′-azido-3′-deoxythymidine and 2′,3′,-dideoxynucleosides inhibit the DNA polymerase gamma by different mechanisms. Biochem Biophys Res Commun 179:776-783.
17. Jedlitschky G, Cassidy AJ, Sales M, Pratt N and Burchell B (1999) Cloning and characterization of a novel human olfactory UDP-glucuronosyltransferase. Biochem J 340:837-843.
18. Jin C, Miners JO, Lillywhite KJ and Mackenzie PI (1993a) Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J Pharmacol Exp Ther 264:475-479.
19. Jin C, Miners JO, Lillywhite KJ and Mackenzie PI (1993b) cDNA cloning and expression of 2 new members of the human liver UDP-glucuronosyltransferase-2B subfamily. Biochem Biophys Res Commun 194:496-503.
20. King CD, Rios GR, Assouline JA and Tephly TR (1999) Expression of UDP-glucuronosyltransferases (UGTs) 2B7 and 1A6 in the human brain and identification of 5-hydroxytryptamine as a substrate. Arch Biochem Biophys 365:156-162.
21. Lavie A, Osterman N, Brundiers R, Goody RS, Jochen R, Manfred K and Schlichting I (1998) Structural basis for efficiency phosphorylation of 3′-azidothymidine monophosphate by Escherichia coli thymidylate kinase. Proc Natl Acad Sci USA 95:14045-14050.
22. Lévesquc É, Beaulieu M, Green MD, Tephly TR, Hum DW and Bélanger A (1997) Isolation and characterization of UGT2B15(D85) a UDP-glucuronosyltransferase encoded by a polymorphic gene. Pharmacogenetics 7:317-325.
23. Lévesque É, Beaulieu M, Hum DW and Bélanger A (1999) Characterization and substrate specificity of UGT2B4(E458) a UDP-glucuronosyltransferase encoded by a polymorphic gene. Pharmacogenetics 9:207-216.
24. Mackenzie PI, Owens IS, Burchell B, Bock KW, Bairoch A, Bélanger A, Foumel-Gigleux S, Green M, Hum DW, Iyanagi T, Lancet D, Louisot P, Magdalou J, Chowdhury JR, Ritter JK, Schachter H, Tephly TR, Tipton KF and Nebert DW (1997) The UDP-glycosyltransferase gene superfamily: Recommended nomenclature update based on evolutionary divergence. Pharmacogenetics 7:255-269.
25. Marchbanks K, Dudley MN, Posner MR and Damowski J (1995) Pharmacokinetics and pharmacodynamics of high-dose zidovudine administered as a continuous infusion in patients with cancer. Pharmacotherapy 15:451-457.
26. Mentre F, Escolano S, Diquet B, Golmard JL and Mallet A (1993) Clinical pharmacokinetics of zidovudine: Inter and intraindividual variability and relationships to long-term efficacy and toxicity. Eur J Clin Pharmacol 45:397-407.
27. Miners JO, McKinnon WM, Lo AC, Kubota T, Ishizaki T and Bhasker R (1998) IXth International Workshop on Glucuronidation and UDP-Glucuronosyltransferases; 1998 Oct 21-23; Brisbane, Australia.
28. Mitsuya H, Yarchoan R and Broder S (1990) Molecular target for AIDS therapy. Science (Wash DC) 249:1533-1544.
29. Moore KH, Raash RH, Brouwer KL, Opheim K, Cheeseman SH, Eyster E, Lemon SM and Van Der Horst CM (1995) Pharmacokinetics and bioavailability of zidovudine in patients with human immunodeficiency virus infection and hepatic disease (AIDS Clinical Trials Group Protocol 062) Antimicrob Agents Chemother 39:2732-2737.
30. Pacifici GM, Evangelisti L, Giuliani L, Metelli RM and Giorani R (1996) Zidovudine glucuronidation in human liver: Interindividual variability. Int J Clin Pharmacol Ther 34:329-334.
31. Patel M, Tang BK, Grant DM and Kalow W (1995) Interindividual variability in the glucuronidation of (S) oxazepam contrasted with that of (R) oxazepam. Pharmacogenetics 5:287-297.
32. Patterson TA, Binienda ZK, Lipe GW, Gillam MP, Slikker W and Sandberg JA (1997) Transplacental pharmacokinetics and fetal distribution of azidothymidine, its glucuronide, and phosphorylated metabolites in late-term rhesus macaques after maternal infusion. Drug Metab Dispos 25:453-459.
33. Rajaonarison JF, Lacarelle B, Catalin J, Placidi M and Rahmadi R (1992) 3,-azido-3,-deoxythymidine drug interactions. Screening for inhibitors in human liver microsomes. Drug Metab Dispos 20:578-584.
34. Taburet AM, Naveau S, Zorza G, Collin JN, Delfraisy JF, Chaput JC and Singlas E (1990) Pharmacokinetics of zidovudine in patient with liver cirrhosis. Clin Pharmacol Ther 47:731-739.