Gender-dependent differences in uridine 5'-diphospho- glucuronosyltransferase have implications in metabolism and clearance of xenobiotics

Expert Opinion on Drug Metabolism and Toxicology

Volumn 9, Issue 12, 2013, Pages 1555-1569

  Liu, Wei ^b   Kulkarni, Kaustubh ^a   Hu, Ming ^c  

^a Frontage Laboratories Inc   (United States)

^b JINAN UNIVERSITY   (China)

^c UNIVERSITY OF HOUSTON   (United States)

Author keywords

Gender difference; Glucuronidation; Metabolic clearance; Sex difference; Sex hormones; Uridine 5 diphospho glucuronosyltransferase

Indexed keywords

BREAST CANCER RESISTANCE PROTEIN; CILOSTAZOL; CUMENE; CYTOCHROME P450 1A2; CYTOCHROME P450 1B1; CYTOCHROME P450 2C11; CYTOCHROME P450 2C12; CYTOCHROME P450 2E1; CYTOCHROME P450 3A1; DAIDZEIN; EMODIN; EZETIMIBE; GENISTEIN; IFOSFAMIDE; ITRACONAZOLE; IVERMECTIN; MORPHINE 3 GLUCURONIDE; MULTIDRUG RESISTANCE PROTEIN 3; MULTIDRUG RESISTANCE PROTEIN 4; MULTIDRUG RESISTANCE PROTEIN 6; PARACETAMOL; PARACETAMOL GLUCURONIDE; PHENOBARBITAL; POLYPHENOL DERIVATIVE; RALOXIFENE; TESTOSTERONE; UNCLASSIFIED DRUG; URIDINE 5' DIPHOSPHO GLUCURONOSYLTRANSFERASE; URIDINE DERIVATIVE; XENOBIOTIC AGENT;

AREA UNDER THE CURVE; BILIARY EXCRETION; COLON; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG EXCRETION; DRUG METABOLISM; DUODENUM; ENTEROHEPATIC CIRCULATION; ESTRUS CYCLE; GLUCURONIDATION; HUMAN; ILEUM; INTESTINE ABSORPTION; INTESTINE PERFUSION; JEJUNUM; LIVER; LIVER MICROSOME; NONHUMAN; PLASMA PROTEIN BINDING; PROTEIN EXPRESSION; REVIEW; SEX DIFFERENCE;

ANIMALS; BIOLOGICAL AVAILABILITY; FEMALE; GLUCURONIDES; GLUCURONOSYLTRANSFERASE; GONADAL STEROID HORMONES; HUMANS; INTESTINES; LIVER; MALE; MICROSOMES, LIVER; SEX CHARACTERISTICS; URIDINE; XENOBIOTICS;

EID: 84888111598     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2013.829040     Document Type: Review

References (51)

1. Kamada N, Yamada K, Odomi M, et al. Sex differences in pharmacokinetics of cilostazol in rats. Xenobiotica 2011;41(10):903-13
2. Coldham NG, Zhang AQ, Key P, Sauer MJ. Absolute bioavailability of [14C] genistein in the rat; plasma pharmacokinetics of parent compound, genistein glucuronide and total radioactivity. Eur J Drug Metab Pharmacokinet 2002;27(4):249-58
3. Kulkarni KH, Yang Z, Niu T, Hu M. Effects of estrogen and estrus cycle on pharmacokinetics, absorption, and disposition of genistein in female Sprague-Dawley rats. J Agric Food Chem 2012;60(32):7949-56
4. Liu W, Tang L, Ye L, et al. Species and gender differences affect the metabolism of emodin via glucuronidation. AAPS J 2010;12(3):424-36
5. Buckley DB, Klaassen CD. Tissue-and gender-specific mRNA expression of UDP-glucuronosyltransferases (UGTs) in mice. Drug Metab Dispos 2007;35(1):121-7
6. Buckley DB, Klaassen CD. Mechanism of gender-divergent UDPglucuronosyltransferase mRNA expression in mouse liver and kidney. Drug Metab Dispos 2009;37(4):834-40
7. Shelby MK, Cherrington NJ, Vansell NR, Klaassen CD. Tissue mRNA expression of the rat UDP-glucuronosyltransferase gene family. Drug Metab Dispos 2003;31(3):326-33
8. Murray HE, Simonian SX, Herbison AE, Gillies GE. Correlation of hypothalamic somatostatin mRNA expression and peptide content with secretion: sexual dimorphism and differential regulation by gonadal factors. J Neuroendocrinol 1999;11(1):27-33
9. Waxman DJ, Holloway MG. Sex differences in the expression of hepatic drug metabolizing enzymes. Mol Pharmacol 2009;76(2):215-28
10. Shimokawa N, Kato Y, Imai K, Wakabayashi K. Changes in content of prolactin mRNA during the rat estrous cycle. Exp Clin Endocrinol 1990;96(1):8-14
11. Lee SY, Oh SJ, Yun KU, et al. Expression of hepatic and ovarian cytochrome P450 during estrous cycle in rats. Arch Toxicol 2012;86(1):75-85
12. Coldham NG, Sauer MJ. Pharmacokinetics of [(14)C]Genistein in the rat: gender-related differences, potential mechanisms of biological action, and implications for human health. Toxicol Appl Pharmacol 2000;164(2):206-15
13. Jiang W, Xu B, Wu B, et al. UDP-glucuronosyltransferase (UGT) 1A9-overexpressing HeLa cells is an appropriate tool to delineate the kinetic interplay between breast cancer resistance protein (BRCP) and UGT and to rapidly identify the glucuronide substrates of BCRP. Drug Metab Dispos 2012;40(2):336-45
14. Kadakol A, Ghosh SS, Sappal BS, et al. Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype. Hum Mutat 2000;16(4):297-306
15. Yang Z, Zhu W, Gao S, et al. Breast cancer resistance protein (ABCG2) determines distribution of genistein Phase II metabolites: reevaluation of the roles of ABCG2 in the disposition of genistein. Drug Metab Dispos 2012;40(10):1883-93
16. Guengerich FP. Uncommon P450-catalyzed reactions. Curr Drug Metab 2001;2(2):93-115
17. Faed EM. Properties of acyl glucuronides: implications for studies of the pharmacokinetics and metabolism of acidic drugs. Drug Metab Rev 1984;15(5-6):1213-49
18. King CD, Rios GR, Green MD, Tephly TR. UDP-glucuronosyltransferases. Curr Drug Metab 2000;1(2):143-61
19. Sorich MJ, Miners JO, McKinnon RA, Smith PA. Multiple pharmacophores for the investigation of human UDP-glucuronosyltransferase isoform substrate selectivity. Mol Pharmacol 2004;65(2):301-8
20. Liu W, Zheng Z, Liu X, et al. Sensitive and robust UPLC-MS/MS method to determine the gender-dependent pharmacokinetics in rats of emodin and its glucuronide. J Pharm Biomed Anal 2011;54(5):1157-62
21. Hamaoka N, Oda Y, Hase I, Asada A. Cytochrome P4502B6 and 2C9 do not metabolize midazolam: kinetic analysis and inhibition study with monoclonal antibodies. Br J Anaesth 2001;86(4):540-4
22. Wang SW, Kulkarni KH, Tang L, et al. Disposition of flavonoids via enteric recycling: UDP-glucuronosyltransferase (UGT) 1As deficiency in Gunn rats is compensated by increases in UGT2Bs activities. J Pharmacol Exp Ther 2009;329(3):1023-31
23. Meng S, Wu B, Singh R, et al. SULT1A3-mediated regiospecific 7-O-sulfation of flavonoids in Caco-2 cells can be explained by the relevant molecular docking studies. Mol Pharm 2012;9(4):862-73
24. Wu B, Basu S, Meng S, et al. Regioselective sulfation and glucuronidation of phenolics: insights into the structural basis. Curr Drug Metab 2011;12(9):900-16
25. Yang Z, Zhu W, Gao S, et al. Simultaneous determination of genistein and its four Phase II metabolites in blood by a sensitive and robust UPLCMS/MS method: application to an oral bioavailability study of genistein in mice. J Pharm Biomed Anal 2010;53(1):81-9
26. Luquita MG, Catania VA, Pozzi EJ, et al. Molecular basis of perinatal changes in UDP-glucuronosyltransferase activity in maternal rat liver. J Pharmacol Exp Ther 2001;298(1):49-56
27. Luquita MG, Catania VA, Sanchez Pozzi EJ, et al. Induction of phase II biotransformation reactions in rat jejunum during lactation. Possible involvement of prolactin. Biochim Biophys Acta 1999;1472(1-2):82-92
28. Luquita MG, Catania VA, Sanchez-Pozzi EJ, Mottino AD. Ovine prolactin increases hepatic UDP-glucuronosyltransferase activity in ovariectomized rats. J Pharmacol Exp Ther 1996;278(2):921-5
29. Mercke Odeberg J, Andrade J, Holmberg K, et al. UGT1A polymorphisms in a Swedish cohort and a human diversity panel, and the relation to bilirubin plasma levels in males and females. Eur J Clin Pharmacol 2006;62(10):829-37
30. Fu ZD, Csanaky IL, Klaassen CD. Effects of aging on mRNA profiles for drug-metabolizing enzymes and transporters in livers of male and female mice. Drug Metab Dispos 2012;40(6):1216-25
31. Chen LJ, Wegerski CJ, Kramer DJ, et al. Disposition and metabolism of cumene in F344 rats and B6C3F1 mice. Drug Metab Dispos 2011;39(3):498-509
32. Baker L, Ratka A. Sex-specific differences in levels of morphine, morphine-3-glucuronide, and morphine antinociception in rats. Pain 2002;95(1-2):65-74
33. Court MH, Krishnaswamy S, Hao Q, et al. Evaluation of 3'-azido-3'-deoxythymidine, morphine, and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B72 polymorphism. Drug Metab Dispos 2003;31(9):1125-33
34. Ishii Y, Takami A, Tsuruda K, et al. Induction of two UDP-glucuronosyltransferase isoforms sensitive to phenobarbital that are involved in morphine glucuronidation: production of isoform-selective antipeptide antibodies toward UGT1.1r and UGT2B1. Drug Metab Dispos 1997;25(2):163-7
35. Alnouti YM, Shelby MK, Chen C, Klaassen CD. Influence of phenobarbital on morphine metabolism and disposition: LC-MS/MS determination of morphine (M) and morphine-3-glucuronide (M3G) in Wistar-Kyoto rat serum, bile, and urine. Curr Drug Metab 2007;8(1):79-89
36. Wang JJ, Lu H, Chan KK. Stereoselective pharmacokinetics of ifosfamide in male and female rats. AAPS Pharm Sci 2000;2(2):E17
37. Court MH. 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 2010;42(1):209-24
38. Court MH. Isoform-selective probe substrates for in vitro studies of human UDP-glucuronosyltransferases. Methods Enzymol 2005;400:104-16
39. Court MH, Hao Q, Krishnaswamy S, et al. UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver. J Pharmacol Exp Ther 2004;310(2):656-65
40. Kosoglou T, Statkevich P, Johnson-Levonas AO, et al. Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet 2005;44(5):467-94
41. Miners JO, Attwood J, Birkett DJ. Influence of sex and oral contraceptive steroids on paracetamol metabolism. Br J Clin Pharmacol 1983;16(5):503-9
42. Available from: http://www.accessdata. fda.gov/drugsatfda-docs/nda/97/ 020815a-bphrev-2.pdf
43. Chen J, Lin H, Hu M. Metabolism of flavonoids via enteric recycling: role of intestinal disposition. J Pharmacol Exp Ther 2003;304(3):1228-35
44. Jia X, Chen J, Lin H, Hu M. Disposition of flavonoids via enteric recycling: enzyme-transporter coupling affects metabolism of biochanin A and formononetin and excretion of their phase II conjugates. J Pharmacol Exp Ther 2004;310(3):1103-13
45. Lu H, Klaassen C. Gender differences in mRNA expression of ATP-binding cassette efflux and bile acid transporters in kidney, liver, and intestine of 5/6 nephrectomized rats. Drug Metab Dispos 2008;36(1):16-23
46. Rost D, Kopplow K, Gehrke S, et al. Gender-specific expression of liver organic anion transporters in rat. Eur J Clin Invest 2005;35(10):635-43
47. MacLean C, Moenning U, Reichel A, Fricker G. Closing the gaps: a full scan of the intestinal expression of p-glycoprotein, breast cancer resistance protein, and multidrug resistance-associated protein 2 in male and female rats. Drug Metab Dispos 2008;36(7):1249-54
48. Lee JK, Abe K, Bridges AS, et al. Sex-dependent disposition of acetaminophen sulfate and glucuronide in the in situ perfused mouse liver. Drug Metab Dispos 2009;37(9):1916-21
49. Lifschitz A, Ballent M, Virkel G, et al. Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation. J Pharm Pharmacol 2006;58(8):1055-62
50. Trottier J, Perreault M, Rudkowska I, et al. Profiling serum bile acid glucuronides in humans: gender divergences, genetic determinants and response to fenofibrate. Clin Pharmacol Ther 2013; [Epub ahead of print]
51. Wittwer E, Kern SE. Role of morphine's metabolites in analgesia: concepts and controversies. AAPS J 2006;8(2):E348-52