Identification of a novel N-carbamoyl glucuronide: In vitro, in vivo, and mechanistic studies

Drug Metabolism and Disposition

Volumn 38, Issue 3, 2010, Pages 361-367

  Gunduz, Mithat ^a   Argikar, Upendra A ^a   Baeschlin, Daniel ^a   Ferreira, Suzie ^a   Hosagrahara, Vinayak ^a   Harriman, Shawn ^a  

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [4 AMINOMETHYL 4 (3 CHLOROPHENYL)CYCLOHEXYL]TETRAHYDROPYRIMIDIN 2 ONE; CARBON 13; CARBON DIOXIDE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; DRUG METABOLITE; GLUCURONOSYLTRANSFERASE; GLUCURONOSYLTRANSFERASE 1A1; GLUCURONOSYLTRANSFERASE 1A3; GLUCURONOSYLTRANSFERASE 2B7; N CARBAMOYLGLUCURONIDE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG GLUCURONIDATION; DRUG STRUCTURE; DRUG TRANSFORMATION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; ISOTOPE LABELING; LIVER MICROSOME; MALE; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; RAT;

ANIMALS; ANTIGENS, CD26; BILE; BIOTRANSFORMATION; CARBAMATES; DIABETES MELLITUS, TYPE 2; ENZYME INHIBITORS; GLUCURONIDES; GLUCURONOSYLTRANSFERASE; HUMANS; ISOENZYMES; MALE; MICROSOMES, LIVER; MOLECULAR STRUCTURE; PYRIMIDINONES; RATS; RATS, SPRAGUE-DAWLEY; SPECIES SPECIFICITY; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; TANDEM MASS SPECTROMETRY; URINE;

CANIS FAMILIARIS; CRICETINAE; RATTUS;

EID: 76749094170     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.109.030650     Document Type: Article

References (29)

1. Argikar UA and Remmel RP (2009a) Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP- glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos 37:229-236.
2. Argikar UA and Remmel RP (2009b) Variation in glucuronidation of lamotrigine in human liver microsomes. Xenobiotica 39:355-363.
3. Beconi MG, Mao A, Liu DQ, Kochansky C, Pereira T, Raab C, Pearson P, and Lee Chiu SH (2003) Metabolism and pharmacokinetics of a dipeptidyl peptidase IV inhibitor in rats, dogs, and monkeys with selective carbamoyl glucuronidation of the primary amine in dogs. Drug Metab Dispos 31:1269-1277.
4. Brown SY, Garland WA, and Fukuda EK (1990) Isolation and characterization of an unusual glucuronide conjugate of rimantadine. Drug Metab Dispos 18:546-547.
5. Burchell B, Brierley CH, Monaghan G, and Clarke DJ (1998) The structure and function of the UDP-glucuronosyltransferase gene family. Adv Pharmacol 42:335-338.
6. Delbressine LP, Funke CW, van Tilborg M, and Kaspersen FM (1990) On the formation of carbamate glucuronides. Xenobiotica 20:133-134.
7. Dow J, Piriou F, Wolf E, Dulery BD, and Haegele KD (1994) Novel carbamate metabolites of mofegiline, a primary amine monoamine oxidase B inhibitor, in dogs and humans. Drug Metab Dispos 22:738-749.
8. Edlund PO and Baranczewski P (2004) Identification of BVT.2938 metabolites by LC/MS and LC/MS/MS after in vitro incubations with liver microsomes and hepatocytes. J Pharm Biomed Anal 34:1079-1090.
9. Elvin AT, Keenaghan JB, Byrnes EW, Tenthorey PA, McMaster PD, Takman BH, Lalka D, Manion CV, Baer DT, Wolshin EM, et al. (1980) Tocainide conjugation in humans: novel biotransformation pathway for a primary amine. J Pharm Sci 69:47-49.
10. Gipple KJ, Chan KT, Elvin AT, Lalka D, and Axelson JE (1982) Species differences in the urinary excretion of the novel primary amine conjugate: tocainide carbamoyl O-beta-D-glucuronide. J Pharm Sci 71:1011-1014.
11. Hayakawa H, Fukushima Y, Kato H, Fukumoto H, Kadota T, Yamamoto H, Kuroiwa H, Nishigaki J, and Tsuji A (2003) Metabolism and disposition of novel des-fluoro quinolone garenoxacin in experimental animals and an interspecies scaling of pharmacokinetic parameters. Drug Metab Dispos 31:1409-1418.
12. Kirsch M, Korth HG, Sustmann R, and de Groot H (2000) Carbon dioxide but not bicarbonate inhibits N-nitrosation of secondary amines. Evidence for amine carbamates as protecting entities. Chem Res Toxicol 13:451-461.
13. Liu DQ, Hop CE, Beconi MG, Mao A, and Chiu SH (2001) Use of on-line hydrogen/deuterium exchange to facilitate metabolite identification. Rapid Commun Mass Spectrom 15:1832-1839.
14. Liu DQ and Pereira T (2002) Interference of a carbamoyl glucuronide metabolite in quantitative liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 16:142-146.
15. 2 adducts of certain amino acids, peptides, and sperm whale myoglobin studied by carbon 13 and proton nuclear magnetic resonance. J Biol Chem 249:7484-7494.
16. Obach RS, Cox LM, and Tremaine LM (2005) Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos 33:262-270.
17. Obach RS, Reed-Hagen AE, Krueger SS, Obach BJ, O'Connell TN, Zandi KS, Miller S, and Coe JW (2006) Metabolism and disposition of varenicline, a selective α4β2 acetylcholine receptor partial agonist, in vivo and in vitro. Drug Metab Dispos 34:121-130.
18. Ramji JV, Keogh JP, Blake TJ, Broom C, Chenery RJ, Citerone DR, Lewis VA, Taylor AC, and Yeulet SE (1999) Disposition of ropinirole in animals and man. Xenobiotica 29:311-325.
19. Remmel RP, Nagar S, and Argikar UA (2007) Conjugative metabolism of drugs, in Drug Metabolism in Drug Design and Development (Zhang D, Zhu M, and Humphreys WG eds) pp 609, Wiley-Interscience, John Wiley and Sons, Inc., Hoboken, NJ.
20. Remmel RP, Zhou J, and Argikar UA (2009) Uridine diphosphoglucuronosyl transferases, in Handbook of Drug Metabolism (Pearson P and Wienkers L eds), pp 630, Informa Health Care, New York.
21. Ronfeld RA, Wolshin EM, and Block AJ (1982) On the kinetics and dynamics of tocainide and its metabolites. Clin Pharmacol Ther 31:384-392.
22. Schaefer WH (1992) Formation of a carbamoyl glucuronide conjugate of carvedilol in vitro using dog and rat liver microsomes. Drug Metab Dispos 20:130-133.
23. Schaefer WH (2006) Reaction of primary and secondary amines to form carbamic acid glucuronides. Curr Drug Metab 7:873-881.
24. Shaffer CL, Gunduz M, O'Connell TN, Obach RS, and Yee S (2005) Biotransformation of a GABAA receptor partial agonist in Sprague-Dawley rats and cynomolgus monkeys: identification of two unique N-carbamoyl metabolites. Drug Metab Dispos 33:1688-1699.
25. Straub K, Davis M, and Hwang B (1988) Benzazepine metabolism revisited. Evidence for the formation of novel amine conjugates. Drug Metab Dispos 16:359-366.
26. Suzuki K and Kamimura H (2007) Pharmacokinetics and metabolism of an α,β-blocker, amosulalol hydrochloride, in mice: biliary excretion of carbamoyl glucuronide. Biol Pharm Bull 30:1580-1585.
27. Tremaine LM, Stroh JG, and Ronfeld RA (1989) Characterization of a carbamic acid ester glucuronide of the secondary amine sertraline. Drug Metab Dispos 17:58-63.
28. Tukey RH and Strassburg CP (2000) Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 40:581-616.
29. 14C]sitagliptin in humans. Drug Metab Dispos 35:533-538.