N-glucuronidation of drugs and other xenobiotics by human and animal UDP-glucuronosyltransferases

Xenobiotica

Volumn 41, Issue 8, 2011, Pages 652-669

  Kaivosaari, Sanna ^a   Finel, Moshe ^b   Koskinen, Mikko ^a  

^a ORION CORPORATION   (Finland)

^b UNIVERSITY OF HELSINKI   (Finland)

Author keywords

amides; amines; aromatic N heterocycles; N glucuronidation; species differences; UDP glucuronosyltransferases; UGT1A4; UGT2B10

Indexed keywords

1 NAPHTHOL; AFLOQUALONE; AMITRIPTYLINE; BENZIDINE DERIVATIVE; BILIRUBIN; CALCITRIOL DERIVATIVE; CARBAMAZEPINE; CARBOXYLIC ACID DERIVATIVE; DEXMEDETOMIDINE; ESTRADIOL; GLUCURONOSYLTRANSFERASE; IMIPRAMINE; KETOTIFEN; LAMOTRIGINE; MEDETOMIDINE; MORPHINE; NICOTINE; OPIATE DERIVATIVE; OXAZEPAM; PERFLUOROOCTANESULFONIC ACID; PHENOL DERIVATIVE; PROPOFOL; RETIGABINE; SEROTONIN; SULFONAMIDE; TAMOXIFEN; TRIFLUOPERAZINE; UNINDEXED DRUG; XENOBIOTIC AGENT; ZIDOVUDINE;

DRUG DISPOSITION; DRUG GLUCURONIDATION; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME SUBSTRATE; HUMAN; NONHUMAN; REVIEW; SPECIES DIFFERENCE;

ANIMALS; CATALYSIS; GLUCURONIDES; GLUCURONOSYLTRANSFERASE; HUMANS; PHARMACEUTICAL PREPARATIONS; URIDINE DIPHOSPHATE; XENOBIOTICS;

ANIMALIA;

EID: 79960140023     PISSN: 00498254     EISSN: 13665928     Source Type: Journal    
DOI: 10.3109/00498254.2011.563327     Document Type: Review

References (107)

1. Alonen A, Finel M, Kostiainen R. (2008).The human UDPglucuronosyltransferase UGT1A3 is highly selective towards N2 in the tetrazole ring of losartan, candesartan, and zolarsartan. Biochem Pharmacol 76:763-772.
2. Bailey MJ, Dickinson RG. (2003).Acyl glucuronide reactivity in perspective: biological consequences. Chem Biol Interact 145:117-137. (Pubitemid 36398426)
3. Berg JZ, Mason J, Boettcher AJ, Hatsukami DK, Murphy SE (2010a) Nicotine metabolism in African Americans and European Americans: variation in glucuronidation by ethnicity and UGT2B10 haplotype. J Pharmacol Exp Ther 332:202-209.
4. Berg JZ, von Weymarn LB, Thompson EA, Wickham KM, Weisensel NA, Hatsukami DK, Murphy SE. (2010b).UGT2B10 genotype influences nicotine glucuronidation, oxidation, and consumption. Cancer Epidemiol Biomarkers Prev 19:1423-1431.
5. Borlak J, Gasparic A, Locher M, Schupke H, Hermann R. (2006). N-glucuronidation of the antiepileptic drug retigabine: results from studies with human volunteers, heterologously expressed human UGTs, human liver, kidney, and liver microsomal membranes of Crigler-Najjar type II. Metab Clin Exp 55:711-721.
6. Breyer-Pfaff U, Fischer D, Winne D. (1997).Biphasic kinetics of quaternary ammonium glucuronide formation from amitriptyline and diphenhydramine in human liver microsomes. Drug Metab Dispos 25:340-345. (Pubitemid 27120580)
7. Breyer-Pfaff U, Mey U, Green MD, Tephly TR. (2000).Comparative N-glucuronidation kinetics of ketotifen and amitriptyline by expressed human UDP-glucuronosyltransferases and liver microsomes. Drug Metab Dispos 28:869-872. (Pubitemid 30612602)
8. Bruck M, Li Q, Lamb JG, Tukey RH. (1997).Characterization of rabbit UDP-glucuronosyltransferase UGT1A7: tertiary amine glucuronidation is catalyzed by UGT1A7 and UGT1A4. Arch Biochem Biophys 348:357-364. (Pubitemid 27344073)
9. Burchell B, Coughtrie MW. (1989).UDP-glucuronosyltransferases. Pharmacol Ther 43:261-289.
10. Burchell B, Lockley DJ, Staines A, Uesawa Y, Coughtrie MW. (2005).Substrate specificity of human hepatic UDPglucuronosyltransferases. Meth Enzymol 400:46-57. (Pubitemid 43052414)
11. Chen G, Blevins-Primeau AS, Dellinger RW, Muscat JE, Lazarus P. (2007).Glucuronidation of nicotine and cotinine by UGT2B10: loss of function by the UGT2B10 Codon 67 (Asp>Tyr) polymorphism. Cancer Res 67:9024-9029. (Pubitemid 47535885)
12. Chen G, Dellinger RW, Gallagher CJ, Sun D, Lazarus P. (2008a). Identification of a prevalent functional missense polymorphism in the UGT2B10 gene and its association with UGT2B10 inactivation against tobacco-specific nitrosamines. Pharmacogenet Genomics 18:181-191. (Pubitemid 351323232)
13. Chen G, Dellinger RW, Sun D, Spratt TE, Lazarus P. (2008b). Glucuronidation of tobacco-specific nitrosamines by UGT2B10. Drug Metab Dispos 36:824-830. (Pubitemid 351574879)
14. Chiu SH, Huskey SW. (1998).Species differences in N-glucuronidation. Drug Metab Dispos 26:838-847.
15. Ciotti M, Lakshmi VM, Basu N, Davis BB, Owens IS, Zenser TV. (1999). Glucuronidation of benzidine and its metabolites by cDNAexpressed human UDP-glucuronosyltransferases and pH stability of glucuronides. Carcinogenesis 20:1963-1969. (Pubitemid 29476124)
16. Clarke DJ, Burchell B. (1994).The uridine diphosphate glucuronosyltransferase multigene family: function and regulation. In: Kaufman FC, ed. Conjugation-Deconjugation Reactions in Drug Metabolism and Toxicity. New York, Springer-Verlag: pp 3-43.
17. Coughtrie MW. (2002).Sulfation through the looking glass- recent advances in sulfotransferase research for the curious. Pharmacogenomics J 2:297-308. (Pubitemid 35439472)
18. Coughtrie MW, Sharp S. (1991).Glucuronidation of imipramine in rabbit and human liver microsomes: assay conditions and interaction with other tertiary amine drugs. Biochem Pharmacol 42:1497-1501.
19. Court MH. (2010).Interindividual variability in hepatic drug glucuronidation: studies into the role of age, sex, enzyme inducers, and genetic polymorphism using the human liver bank as a model system. Drug Metab Rev 42:209-224.
20. Court MH. (2005).Isoform-selective probe substrates for in vitro studies of human UDP-glucuronosyltransferases. Meth Enzymol 400:104-116. (Pubitemid 43052418)
21. Court MH, Greenblatt DJ. (2000).Molecular genetic basis for deficient acetaminophen glucuronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms. Pharmacogenetics 10:355-369. (Pubitemid 30345183)
22. Court MH, Hazarika S, Krishnaswamy S, Finel M, Williams JA. (2008).Novel polymorphic human UDP-glucuronosyltransferase 2A3: cloning, functional characterization of enzyme variants, comparative tissue expression, and gene induction. Mol Pharmacol 74:744-754.
23. Dahl-Puustinen ML, Aberg-Wistedt A, Bertilsson L. (1989). Glucuronidation of amitriptyline in man in vivo. Pharmacol Toxicol 65:37-39. (Pubitemid 19174476)
24. Dellinger RW, Chen G, Blevins-Primeau AS, Krzeminski J, Amin S, Lazarus P. (2007).Glucuronidation of PhIP and N-OH-PhIP by UDP-glucuronosyltransferase 1A10. Carcinogenesis 28:2412-2418. (Pubitemid 350111602)
25. Ebner T, Burchell B. (1993).Substrate specificities of two stably expressed human liver UDP-glucuronosyltransferases of the UGT1 gene family. Drug Metab Dispos 21:50-55. (Pubitemid 23052221)
26. Finel M, Li X, Gardner-Stephen D, Bratton S, Mackenzie PI, Radominska- Pandya A. (2005).Human UDP-glucuronosyltransferase 1A5: identification, expression, and activity. J Pharmacol Exp Ther 315:1143-1149. (Pubitemid 41635401)
27. Gamage N, Barnett A, Hempel N, Duggleby RG, Windmill KF, Martin JL, McManus ME. (2006).Human sulfotransferases and their role in chemical metabolism. Toxicol Sci 90:5-22. (Pubitemid 43264722)
28. Ghosheh O, Hawes EM. (2002).Microsomal N-glucuronidation of nicotine and cotinine: human hepatic interindividual, human intertissue, and interspecies hepatic variation. Drug Metab Dispos 30:1478-1483. (Pubitemid 35402058)
29. Girard H, Thibaudeau J, Court MH, Fortier LC, Villeneuve L, Caron P, Hao Q, von Moltke LL, Greenblatt DJ, Guillemette C. (2005). UGT1A1 polymorphisms are important determinants of dietary carcinogen detoxification in the liver. Hepatology 42:448-457. (Pubitemid 41061098)
30. Green MD, Bishop WP, Tephly TR. (1995).Expressed human UGT1.4 protein catalyzes the formation of quaternary ammonium-linked glucuronides. Drug Metab Dispos 23:299-302.
31. Green MD, King CD, Mojarrabi B, Mackenzie PI, Tephly TR. (1998). Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP-glucuronosyltransferase 1A3. Drug Metab Dispos 26:507-512. (Pubitemid 28498354)
32. Green MD, Tephly TR. (1996).Glucuronidation of amines and hydroxylated xenobiotics and endobiotics catalyzed by expressed human UGT1.4 protein. Drug Metab Dispos 24:356-363. (Pubitemid 26089830)
33. Green MD, Tephly TR. (1998).Glucuronidation of amine substrates by purified and expressed UDP-glucuronosyltransferase proteins. Drug Metab Dispos 26:860-867. (Pubitemid 28452052)
34. Guengerich FP. (2008).Oxidative, reductive and hydrolytic metabolism of drugs. In: Zhang D, Zhu M, Humphreys WG, eds. Drug Metabolism in Drug Design and Development. Hoboken, New Jersey, Wiley Interscience: pp 15-36.
35. Hawes EM. (1998).N+-glucuronidation, a common pathway in human metabolism of drugs with a tertiary amine group. Drug Metab Dispos 26:830-837. (Pubitemid 28452048)
36. Hempel R, Schupke H, McNeilly PJ, Heinecke K, Kronbach C, Grunwald C, Zimmermann G, Griesinger C, Engel J, Kronbach T. (1999). Metabolism of retigabine (D-23129), a novel anticonvulsant. Drug Metab Dispos 27:613-622. (Pubitemid 29214474)
37. Hukkanen J, Jacob P 3rd, Benowitz NL. (2005).Metabolism and disposition kinetics of nicotine. Pharmacol Rev 57:79-115. (Pubitemid 40283970)
38. Ikushiro S, Emi Y, Iyanagi T. (1995).Identification and analysis of drugresponsive expression of UDP-glucuronosyltransferase family 1 (UGT1) isozyme in rat hepatic microsomes using anti-peptide antibodies. Arch Biochem Biophys 324:267-272.
39. Itho K, Mackenzie PI, Ikushiro S, Miners JO, Finel M. (2008).The configuration of the 17-hydroxy group variably influences the glucuronidation of beta-estradiol and epiestradiol by human UDPglucuronosyltransferases. Drug Metab Dispos 36:2307-2315.
40. Izukawa T, Nakajima M, Fujiwara R, Yamanaka H, Fukami T, Takamiya M, Aoki Y, Ikushiro S, Sakaki T, Yokoi T. (2009).Quantitative analysis of UDP-glucuronosyltransferase (UGT) 1A and UGT2B expression levels in human livers. Drug Metab Dispos 37:1759-1768.
41. Jedlitschky G, Cassidy AJ, Sales M, Pratt N, Burchell B. (1999). Cloning and characterization of a novel human olfactory UDPglucuronosyltransferase. Biochem J 340 (Pt 3):837-843. (Pubitemid 29312884)
42. Kaderlik KR, Mulder GJ, Turesky RJ, Lang NP, Teitel CH, Chiarelli MP, Kadlubar FF. (1994).Glucuronidation of N-hydroxy heterocyclic amines by human and rat liver microsomes. Carcinogenesis 15:1695-1701. (Pubitemid 24262161)
43. Kaivosaari S, Toivonen P, Aitio O, Sipil•J, Koskinen M, Salonen JS, Finel M. (2008).Regio- and stereospecific N-glucuronidation of medetomidine: the differences between UDP glucuronosyltransferase (UGT) 1A4 and UGT2B10 account for the complex kinetics of human liver microsomes. Drug Metab Dispos 36:1529-1537.
44. Kaivosaari S, Toivonen P, Hesse LM, Koskinen M, Court MH, Finel M. (2007).Nicotine glucuronidation and the human UDPglucuronosyltransferase UGT2B10. Mol Pharmacol 72:761-768. (Pubitemid 47347311)
45. Kaji H, Kume T. (2005).Characterization of afloqualone N-glucuronidation: species differences and identification of human UDP-glucuronosyltransferase isoform(s).Drug Metab Dispos 33:60-67. (Pubitemid 40023515)
46. Kaku T, Ogura K, Nishiyama T, Ohnuma T, Muro K, Hiratsuka A. (2004). Quaternary ammonium-linked glucuronidation of tamoxifen by human liver microsomes and UDP-glucuronosyltransferase 1A4. Biochem Pharmacol 67:2093-2102. (Pubitemid 38595490)
47. Kassahun K, Mattiuz E, Franklin R, Gillespie T. (1998).Olanzapine 10-N-glucuronide. A tertiary N-glucuronide unique to humans. Drug Metab Dispos 26:848-855. (Pubitemid 28452050)
48. Kerdpin O, Mackenzie PI, Bowalgaha K, Finel M, Miners JO. (2009).Influence of N-terminal domain histidine and proline residues on the substrate selectivities of human UDPglucuronosyltransferase 1A1, 1A6, 1A9, 2B7, and 2B10. Drug Metab Dispos 37:1948-1955.
49. Kilford PJ, Stringer R, Sohal B, Houston JB, Galetin A. (2009).Prediction of drug clearance by glucuronidation from in vitro data: use of combined cytochrome P450 and UDP-glucuronosyltransferase cofactors in alamethicin-activated human liver microsomes. Drug Metab Dispos 37:82-89.
50. King CD, Green MD, Rios GR, Coffman BL, Owens IS, Bishop WP, Tephly TR. (1996).The glucuronidation of exogenous and endogenous compounds by stably expressed rat and human UDP-glucuronosyltransferase 1.1. Arch Biochem Biophys 332:92-100. (Pubitemid 26286137)
51. King CD, Rios GR, Green MD, Tephly TR. (2000). UDPglucuronosyltransferases. Curr Drug Metab 1:143-161.
52. Klieber S, Hugla S, Ngo R, Arabeyre-Fabre C, Meunier V, Sadoun F, Fedeli O, Rival M, Bourrie M, Guillou F, Maurel P, Fabre G. (2008). Contribution of the N-glucuronidation pathway to the overall in vitro metabolic clearance of midazolam in humans. Drug Metab Dispos 36:851-862. (Pubitemid 351574882)
53. Kuehl GE, Lampe JW, Potter JD, Bigler J. (2005).Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos 33:1027-1035. (Pubitemid 41002785)
54. Lautala P, Ethell BT, Taskinen J, Burchell B. (2000).The specificity of glucuronidation of entacapone and tolcapone by recombinant human UDP-glucuronosyltransferases. Drug Metab Dispos 28:1385-1389.
55. Lautala P, Kivimaa M, Salomies H, Elovaara E, Taskinen J. (1997). Glucuronidation of entacapone, nitecapone, tolcapone, and some other nitrocatechols by rat liver microsomes. Pharm Res 14:1444-1448. (Pubitemid 27481077)
56. Lin J, Sahakian DC, de Morais SM, Xu JJ, Polzer RJ, Winter SM. (2003). The role of absorption, distribution, metabolism, excretion and toxicity in drug discovery. Curr Top Med Chem 3:1125-1154.
57. Luo H, Hawes EM, McKay G, Korchinski ED, Midha KK. (1991). N(+)-glucuronidation of aliphatic tertiary amines, a general phenomenon in the metabolism of H1-antihistamines in humans. Xenobiotica 21:1281-1288.
58. Luo H, Hawes EM, McKay G, Korchinski ED, Midha KK. (1995). N(+)-glucuronidation of aliphatic tertiary amines in human: antidepressant versus antipsychotic drugs. Xenobiotica 25:291-301.
59. Luukkanen L, Taskinen J, Kurkela M, Kostiainen R, Hirvonen J, Finel M. (2005).Kinetic characterization of the 1A subfamily of recombinant human UDP-glucuronosyltransferases. Drug Metab Dispos 33:1017-1026. (Pubitemid 41002784)
60. Mackenzie PI, Bock KW, Burchell B, Guillemette C, Ikushiro S, Iyanagi T, Miners JO, Owens IS, Nebert DW. (2005).Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenet Genomics 15:677-685. (Pubitemid 41345319)
61. Mackenzie PI, Gregory PA, Gardner-Stephen DA, Lewinsky RH, Jorgensen BR, Nishiyama T, Xie W, Radominska-Pandya A. (2003). Regulation of UDP glucuronosyltransferase genes. Curr Drug Metab 4:249-257. (Pubitemid 36656482)
62. Magdalou J, Herber R, Bidault R, Siest G. (1992).In vitro N-glucuronidation of a novel antiepileptic drug, lamotrigine, by human liver microsomes. J Pharmacol Exp Ther 260:1166-1173.
63. Mey U, Wachsmuth H, Breyer-Pfaff U. (1999).Conjugation of the enantiomers of ketotifen to four isomeric quaternary ammonium glucuronides in humans in vivo and in liver microsomes. Drug Metab Dispos 27:1281-1292.
64. Miners JO, Knights KM, Houston JB, Mackenzie PI. (2006).In vitroin vivo correlation for drugs and other compounds eliminated by glucuronidation in humans: pitfalls and promises. Biochem Pharmacol 71:1531-1539.
65. Miners JO, Mackenzie PI. (1991).Drug glucuronidation in humans. Pharmacol Ther 51:347-369.
66. Nakajima M, Tanaka E, Kobayashi T, Ohashi N, Kume T, Yokoi T. (2002).Imipramine N-glucuronidation in human liver microsomes: biphasic kinetics and characterization of UDPglucuronosyltransferase isoforms. Drug Metab Dispos 30:636-642. (Pubitemid 34579095)
67. Nakazawa T, Miyata K, Omura K, Iwanaga T, Nagata O. (2006). Metabolic profile of FYX-051 (4-(5-pyridin-4-yl-1h-[1,2,4]triazol- 3-yl)pyridine-2- carbonitrile) in the rat, dog, monkey, and human: identification of N-glucuronides and N-glucosides. Drug Metab Dispos 34:1880-1886. (Pubitemid 44771717)
68. Nishimura M, Naito S. (2006).Tissue-specific mRNA expression profiles of human phase I metabolizing enzymes except for cytochrome P450 and phase II metabolizing enzymes. Drug Metab Pharmacokinet 21:357-374.
69. Ohno S, Nakajin S. (2009).Determination of mRNA expression of human UDP-glucuronosyltransferases and application for localization in various human tissues by real-time reverse transcriptase-polymerase chain reaction. Drug Metab Dispos 37:32-40.
70. Omura K, Nakazawa T, Sato T, Iwanaga T, Nagata O. (2007). Characterization of N-glucuronidation of 4-(5-pyridin-4-yl- 1H-[1,2,4]triazol-3- yl) pyridine-2-carbonitrile (FYX-051): a new xanthine oxidoreductase inhibitor. Drug Metab Dispos 35:2143-2148. (Pubitemid 350146198)
71. Ouzzine M, Barr•L, Netter P, Magdalou J, Fournel-Gigleux S. (2003). The human UDP-glucuronosyltransferases: structural aspects and drug glucuronidation. Drug Metab Rev 35:287-303. (Pubitemid 38018108)
72. Pelkonen O. (2002).Human CYPs: in vivo and clinical aspects. Drug Metab Rev 34:37-46. (Pubitemid 34311086)
73. Pelkonen O, Kapitulnik J, Gundert-Remy U, Boobis AR, Stockis A. (2008).Local kinetics and dynamics of xenobiotics. Crit Rev Toxicol 38:697-720.
74. Remmel RP, Nagar S, Argikar U. (2008).Conjugative metabolism of drugs. In: Zhang D, Zhu M and Humphreys WG eds. Drug Metabolism in Drug Design and Development. Hoboken, New Jersey, Wiley Interscience: pp 37-62.
75. Rowland A, Elliot DJ, Williams JA, Mackenzie PI, Dickinson RG, Miners JO. (2006).In vitro characterization of lamotrigine N2-glucuronidation and the lamotrigine-valproic acid interaction. Drug Metab Dispos 34:1055-1062. (Pubitemid 43763765)
76. Rush WR, Alexander OF, Hall DJ, Dow RJ, Tokes L, Kurz L, Graham DJ. (1990).The metabolism of nafimidone hydrochloride in the dog, primates and man. Xenobiotica 20:123-132. (Pubitemid 20044706)
77. Sallustio BC, Sabordo L, Evans AM, Nation RL. (2000).Hepatic disposition of electrophilic acyl glucuronide conjugates. Curr Drug Metab 1:163-180.
78. Senafi SB, Clarke DJ, Burchell B. (1994).Investigation of the substrate specificity of a cloned expressed human bilirubin UDPglucuronosyltransferase: UDP-sugar specificity and involvement in steroid and xenobiotic glucuronidation. Biochem J 303 (Pt 1):233-240. (Pubitemid 24302924)
79. Shiratani H, Katoh M, Nakajima M, Yokoi T. (2008).Species differences in UDP-glucuronosyltransferase activities in mice and rats. Drug Metab Dispos 36:1745-1752.
80. Singh SS. (2006).Preclinical pharmacokinetics: an approach towards safer and efficacious drugs. Curr Drug Metab 7:165-182.
81. Sinz MW, Remmel RP. (1991).Isolation and characterization of a novel quaternary ammonium-linked glucuronide of lamotrigine. Drug Metab Dispos 19:149-153.
82. Sneitz N, Court MH, Zhang X, Laajanen K, Yee KK, Dalton P, Ding X, Finel M. (2009).Human UDP-glucuronosyltransferase UGT2A2: cDNA construction, expression, and functional characterization in comparison with UGT2A1 and UGT2A3. Pharmacogenet Genomics 19:923-934.
83. Soars MG, Burchell B, Riley RJ. (2002).In vitro analysis of human drug glucuronidation and prediction of in vivo metabolic clearance. J Pharmacol Exp Ther 301:382-390. (Pubitemid 34250317)
84. Soars MG, Fettes M, O'Sullivan AC, Riley RJ, Ethell BT, Burchell B. (2003).Cloning and characterisation of the first drug-metabolising canine UDP-glucuronosyltransferase of the 2B subfamily. Biochem Pharmacol 65:1251-1259. (Pubitemid 36407777)
85. Soars MG, Riley RJ, Burchell B. (2001a).Evaluation of the marmoset as a model species for drug glucuronidation. Xenobiotica 31:849-860. (Pubitemid 34074788)
86. Soars MG, Riley RJ, Findlay KA, Coffey MJ, Burchell B. (2001b).Evidence for significant differences in microsomal drug glucuronidation by canine and human liver and kidney. Drug Metab Dispos 29:121-126. (Pubitemid 32112924)
87. Staines AG, Coughtrie MW, Burchell B. (2004).N-glucuronidation of carbamazepine in human tissues is mediated by UGT2B7. J Pharmacol Exp Ther 311:1131-1137. (Pubitemid 39612720)
88. Sten T, Bichlmaier I, Kuuranne T, Leinonen A, Yli-Kauhaluoma J, Finel M. (2009).UDP-glucuronosyltransferases (UGTs) 2B7 and UGT2B17 display converse specificity in testosterone and epitestosterone glucuronidation, whereas UGT2A1 conjugates both androgens similarly. Drug Metab Dispos 37:417-423.
89. Stevens JC, Fayer JL, Cassidy KC. (2001).Characterization of 2-[[4- [[2-(1H-tetrazol-5-ylmethyl)phenyl]methoxy]methyl]quinoline N-glucuronidation by in vitro and in vivo approaches. Drug Metab Dispos 29:289-295. (Pubitemid 32179529)
90. Stone AN, Mackenzie PI, Galetin A, Houston JB, Miners JO. (2003).Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human UDP-glucuronosyltransferases: evidence for atypical glucuronidation kinetics by UGT2B7. Drug Metab Dispos 31:1086-1089. (Pubitemid 37048278)
91. Tsai MC, Gorrod JW. (1999).Evidence for the biosynthesis of A glucuronide conjugate of (S)-(-)-nicotine, but not (S)-(-)- cotinine or (+/-)-trans-3'-hydroxycotinine by marmoset hepatic microsomes. Drug Metabol Drug Interact 15:223-237.
92. Tukey RH, Strassburg CP. (2000).Human UDPglucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 40:581-616. (Pubitemid 30340694)
93. Turgeon D, Carrier JS, Lesque E, Hum DW, Banger A. (2001). Relative enzymatic activity, protein stability, and tissue distribution of human steroid-metabolizing UGT2B subfamily members. Endocrinology 142:778-787. (Pubitemid 32222427)
94. Uchaipichat V, Mackenzie PI, Elliot DJ, Miners JO. (2006).Selectivity of substrate (trifluoperazine) and inhibitor (amitriptyline, androsterone, canrenoic acid, hecogenin, phenylbutazone, quinidine, quinine, and sulfinpyrazone) "probes" for human UDPglucuronosyltransferases. Drug Metab Dispos 34:449-456.
95. Uesawa Y, Staines AG, Lockley D, Mohri K, Burchell B. (2007). Identification of the human liver UDP-glucuronosyltransferase involved in the metabolism of p-ethoxyphenylurea (dulcin).Arch Toxicol 81:163-168. (Pubitemid 46364904)
96. Uesawa Y, Staines AG, O'Sullivan A, Mohri K, Burchell B. (2004). Identification of the rabbit liver UDP-glucuronosyltransferase catalyzing the glucuronidation of 4-ethoxyphenylurea (dulcin). Drug Metab Dispos 32:1476-1481. (Pubitemid 39564569)
97. Vashishtha SC, Hawes EM, McCann DJ, Ghosheh O, Hogg L. (2002). Quaternary ammonium-linked glucuronidation of 1-substituted imidazoles by liver microsomes: interspecies differences and structuremetabolism relationships. Drug Metab Dispos 30:1070-1076.
98. Wells PG, Mackenzie PI, Chowdhury JR, Guillemette C, Gregory PA, Ishii Y, Hansen AJ, Kessler FK, Kim PM, Chowdhury NR, Ritter JK. (2004).Glucuronidation and the UDP-glucuronosyltransferases in health and disease. Drug Metab Dispos 32:281-290. (Pubitemid 38263885)
99. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE. (2004).Drug-drug interactions for UDP- glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos 32:1201-1208. (Pubitemid 39410902)
100. Xu L, Krenitsky DM, Seacat AM, Butenhoff JL, Tephly TR, Anders MW. (2006).N-glucuronidation of perfluorooctanesulfonamide by human, rat, dog, and monkey liver microsomes and by expressed rat and human UDP- glucuronosyltransferases. Drug Metab Dispos 34:1406-1410. (Pubitemid 44079883)
101. Yan Z, Caldwell GW, Gauthier D, Leo GC, Mei J, Ho CY, Jones WJ, Masucci JA, Tuman RW, Galemmo RA Jr, Johnson DL. (2006). N-glucuronidation of the platelet-derived growth factor receptor tyrosine kinase inhibitor 6,7-(dimethoxy-2,4-dihydroindeno[1,2- C]pyrazol-3-yl)-(3-fluoro-phenyl)-amine by human UDPglucuronosyltransferases. Drug Metab Dispos 34:748-755.
102. Yin H, Bennett G, Jones JP. (1994).Mechanistic studies of uridine diphosphate glucuronosyltransferase. Chem Biol Interact 90:47-58. (Pubitemid 24087506)
103. Zamek-Gliszczynski MJ, Hoffmaster KA, Nezasa K, Tallman MN, Brouwer KL. (2006).Integration of hepatic drug transporters and phase II metabolizing enzymes: mechanisms of hepatic excretion of sulfate, glucuronide, and glutathione metabolites. Eur J Pharm Sci 27:447-486. (Pubitemid 43363339)
104. Zenser TV, Lakshmi VM, Davis BB. (1998).N-glucuronidation of benzidine and its metabolites. Role in bladder cancer. Drug Metab Dispos 26:856-859. (Pubitemid 28452051)
105. Zenser TV, Lakshmi VM, Hsu FF, Davis BB. (2002).Metabolism of N-acetylbenzidine and initiation of bladder cancer. Mutat Res 506- 507:29-40. (Pubitemid 35286537)
106. Zhang D, Zhao W, Roongta VA, Mitroka JG, Klunk LJ, Zhu M. (2004). Amide N-glucuronidation of MaxiPost catalyzed by UDPglucuronosyltransferase 2B7 in humans. Drug Metab Dispos 32:545-551. (Pubitemid 38535033)
107. Zhou D, Guo J, Linnenbach AJ, Booth-Genthe CL, Grimm SW. (2010).Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine. Drug Metab Dispos 38:863-870.