The N+-glucuronidation, a common pathway in human metabolism of drugs with a tertiary amine group

Drug Metabolism and Disposition

Volumn 26, Issue 9, 1998, Pages 830-837

  Hawes, Edward M ^a  

^a UNIVERSITY OF SASKATCHEWAN   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIZINE; CYCLOBENZAPRINE; CYPROHEPTADINE; DOXEPIN; KETOTIFEN; LAMOTRIGINE; MIANSERIN; TIOCONAZOLE; XENOBIOTIC AGENT;

CONFERENCE PAPER; DRUG EXCRETION; DRUG GLUCURONIDATION; DRUG METABOLISM; DRUG STRUCTURE; HUMAN; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; URINARY EXCRETION; XENOBIOTIC METABOLISM;

AMINES; ANIMALS; GLUCURONATES; HUMANS; PHARMACEUTICAL PREPARATIONS; XENOBIOTICS;

EID: 0031661763     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Conference Paper

References (69)

1. Aboul-Enein HY (1977) Synthesis of β-D-glucuronopyranosylpyridinium bromide. J Carbohydr Nucleosides Nucleotides 4:77-81.
2. Babu SR, Lakshmi VM, Hsu FF, Zenser TV and Davis BB (1992) Role of N-glucuronidation in benzidine-induced bladder cancer in dog. Carcinogenesis 13:1235-1240.
3. Becher B, Fischer W, Taneri Z, Scholz E, Müller WE and Breyer-Pfaff U (1992) Urinary metabolites of amitriptylinoxide and amitriptyline in single-dose experiments and during continuous therapy. Psychopharmacology 106:303-310.
4. Beckett AH and Ali HM (1978) Metabolic oxidation of a tertiary amine to produce a N-glucuronide, in Proceedings of the Second International Symposium on the Biological Oxidation of Nitrogen in Organic Molecules (Gorrod JW ed) pp 101-107, Elsevier/North Holland Biomedical Press, London.
5. Beider A, Decouvelaere B, Gaillard C, Depaire H, Heusse D, Ledoux C, Lemar M, Le Roy JP, Raynaud L, Snozzi C and Gregoire J (1983) Comparison of the metabolism of oltipraz in the mouse, rat and monkey and in man. Arzneim Forsch 33:1289-1297.
6. Breyer-Pfaff U, Becher B, Nusser R, Nill K, Baier-Weber B, Zaunbrecher D, Wachsmuth H and Prox A (1990) Quaternary N-glucuronides of 10-hydroxylated amitriptyline metabolites in human urine. Xenobiotica 20:727-738.
7. Byrd GD, Chang K-M, Greene JM and deBethizy JD (1992) Evidence for urinary excretion of glucuronide conjugates of nicotine, cotinine, and trans-3-hydroxycotinine in smokers. Drug Metab Dispos 20:192-197.
8. Byrd GD, Uhrig MS, deBethizy JD, Caldwell WS, Crooks PA, Ravard A and Riggs RM (1994) Direct determination of cotinine-N-glucuronide in urine using thermospray liquid chromatography/mass spectrometry. Biol Mass Spectrom 23:103-107.
9. Caldwell J (1985) Glucuronic acid conjugation in the context of the metabolic conjugation of xenobiotics, in Advances in Glucuronide Conjugation (Matern S, Bock KW and Gerok W eds) pp 7-20, MTP Press Limited, Lancaster.
10. Caldwell WS, Greene JM, Byrd GD, Chang KM, Uhrig MS, deBethizy JD, Crooks PA, Bhatti BS and Riggs RM (1992) Characterization of the glucuronide conjugates of cotinine: A previously unidentified major metabolite of nicotine in smokers' urine. Chem Res Toxicol 5:280-285.
11. Chaudhary AK, Hubbard JW, McKay G and Midha KK (1988) Identification of a quaternary ammonium-linked glucuronide of chlorpromazine in the urine of a schizophrenic patient treated with chlorpromazine. Drug Metab Dispos 16:506-508.
12. Chaudhuri NK, Servando OA, Manniello MJ, Luders RC, Chao DK and Bartlett MF (1976) Metabolism of tripelennamine in man. Drug Metab Dispos 4:372-378.
13. Chiu S-HL and Huskey S-EW (1998) Species differences in N-glucuronidation. Drug Metab Dispos 26:838-847.
14. Chung BC, Kim DH, Jung BH, Eom K, Slikker W Jr and Park J (1994) Identification of urinary metabolites of pyrilamine after oral administration to man. Xenobiotica 24:451-459.
15. Cohen AF, Land GS, Breimer DD, Yuen WC. Winton C and Peck AW (1987) Lamotrigine, a new anticonvulsant: Pharmacokinetics in normal humans. Clin Pharmacol Ther 42:535-541.
16. Colletti AE and Krieter PA (1994) Disposition of the angiotensin II receptor antagonist L-158, 809 in rats and rhesus monkey. Drug Metab Dispos 22:183-188.
17. Dahl-Puustinen M-L, Aberg-Wistedt A and Bertilsson L (1989) Glucuronidation of amitriptyline in man in vivo. Pharmacol Toxicol 65:37-39.
18. Dahl-Puustinen M-L and Bertilsson L (1987) Formation of a quaternary N-glucuronide of amitriptyline in human liver microsomes. Pharmacol Toxicol 61:342-346.
19. Dalgaard L (1983) Preparation and hydrolysis of N-glucuronides of pyridine and piperidine. Acta Chem Scand B 37:923-928.
20. Delbressine LPC, Moonen MEG, Kaspersen FM, Jacobs PL and Wagenaars GL (1992) Biotransformation of mianserin in laboratory animals and man. Xenobiotica 22:227-236.
21. Dulik DM and Fenselau C (1987) Species-dependent glucuronidation of drugs by immobilized rabbit, rhesus monkey and human UDP-glucuronyltransferases. Drug Metab Dispos 15:473-477.
22. Dutton GJ (1980) Structure and properties of glucuronides, in Glucuronidation of Drugs and Other Compounds, pp 14-15, CRC Press, Boca Raton, Fla.
23. Fenselau C, Yelle L, Stogniew M, Liberato D, Lehman J, Feng P and Colvin M Jr (1983) Analysis of glucuronides by fast atom bombardment. Int J Mass Spectrom Ion Phys 46:411-414.
24. Fischer LJ, Thies RL, Charkowski D and Donham KJ (1980) Formation of urinary excretion of cyproheptadine glucuronide in monkeys, chimpanzees, and humans. Drug Metab Dispos 8:422-424.
25. Green MD and Tephly TR (1996) Glucuronidation of amines and hydroxylated xenobiotics and enobiotics catalysed by expressed human UGT1.4 protein. Drug Metab Dispos 24:356-363.
26. Green MD and Tephly TR ( 1998) Glucuronidation of amine substrates by purified and expressed UDP-glucuronosyltransferase proteins. Drug Metab Dispos 26:860-867.
27. Guerret M, Julien-Larose C and Lavene D (1981) Application of capillary column gas chromatography to the elucidation of the metabolism of ketotifen in the monkey and man. C R Congr Eur Biopharm Pharmacokinet 1st 2:317-321.
28. Hucker HB, Balletto AJ, Arison BH and Zacchei AG (1978a) Metabolism of cyclobenzaprine in the dog. Drug Metab Dispos 6:184-192.
29. Hucker HB, Stauffer SC, Balletto AJ, White SD, Zacchei AG and Arison BH (1978b) Physiological disposition and metabolism of cyclobenzaprine in the rat, dog, rhesus monkey, and man. Drug Metab Dispos 6:659-672.
30. Huskey SW, Doss GA, Miller RR, Schoen WR and Chiu S-HL (1994a) N-glucuronidation reactions. II. Relative N-glucuronidation reactivity of methylbiphenyl tetrazole, methylbiphenyl triazole, and methylbiphenyl imidazole in rat, monkey, and human hepatic microsomes. Drug Metab Dispos 22:651-658.
31. Huskey SW, Magdalou J, Ouzzine M, Siest G and Chiu S-HL (1994b) N-glucuronidation reactions. III. Regioselectivity of N-glucuronidation of methylbiphenyl tetrazole, methylbiphenyl triazole, and methylbiphenyl imidazole using human and rat recombinant UDP-glucuronosyltransferases stably expressed in V79 cells. Drug Metab Dispos 22:659-662.
32. Huskey SW, Miller RR and Chiu S-HL (1993) N-Glucuronidation reactions. I. Tetrazole N-glucuronidation of selected angiotensin II receptor antagonists in hepatic microsomes from rats, dogs, monkeys, and humans. Drug Metab Dispos 21:792-799.
33. Janssen FW, Kirkman SK, Fenselau C, Stogniew M, Hofmann BR, Young EM and Ruelius HW (1982) Metabolic formation of N-and O-glucuronides of 3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid: Rearrangement of the 1-O-acyl glucuronide. Drug Metab Dispos 10:599-604.
34. Julien-Larose C, Guerret M, Lavene D and Kiechel JR (1983) Quantification of ketotifen and its metabolites in human plasma by gas chromatography-mass spectrometry. Biomed Mass Spectrom 10:136-142.
35. Kaspersen FM and Van Boeckel CAA ( 1987) A review of the methods of chemical synthesis of sulphate and glucuronide conjugates. Xenobiotica 17:1451-1471.
36. Kassahun K, Mattiuz E, Franklin R and Gillespie T (1998) Olanzapine 10-N-glucuronide: A tertiary N-glucuronide unique to humans. Drug Metab Dispos 26:848-855.
37. Kawahara K, Awaji T, Uda K, Sakai Y and Hashimoto Y ( 1986) Urinary excretion of conjugates of dothiepin and northiaden (mono-N-demethyldothiepin) after an oral dose of dothiepin to humans. Eur J Drug Metab Pharmacokinet 11:29-32.
38. Kennedy KA, Halmi KA and Fischer LJ (1977) Urinary excretion of a quaternary ammonium glucuronide metabolite of cyproheptadine in humans undergoing chronic drug therapy. Life Sci 21:1813-1820.
39. Le Bigot JF, Begue JM, Kiechel JR and Guillouzo A (1987) Species differences in metabolism of ketotifen in rat, rabbit and man: Demonstration of similar pathways in vivo and in cultured hepatocytes. Life Sci 40:883-890.
40. Lehman JP and Fenselau C (1982) Synthesis of quaternary ammonium-linked glucuronides by rabbit hepatic microsomal UDP-glucuronyltransferase and analysis by fast-atom bombardment mass spectrometry. Drug Metab Dispos 10:446-449.
41. Lehman JP, Fenselau C and Depaulo JR (1983) Quaternary ammonium-linked glucuronides of amitriptyline, imipramine, and chlorpromazine. Drug Metab Dispos 11:221-225.
42. Lehman JP, Ferrin L, Fenselau C and Yost GS (1981) Simultaneous immobilization of cytochrome P-450 and glucuronyltransferase for synthesis of drug metabolites. Drug Metab Dispos 9:15-18.
43. 1-antihistamines in humans. Xenobiotica 21:1281-1288.
44. Luo H, Hawes EM, McKay G, Korchinski ED and Midha KK (1991b) The quaternary ammonium-linked glucuronide of doxepin: A major metabolite in depressed patients treated with doxepin. Drug Metab Dispos 19:722-724.
45. Luo H, Hawes EM, McKay G, Korchinski ED and Midha KK (1992a) The quaternary ammonium-linked glucuronide metabolite of cyclizine is excreted in human feces. Pharm Res 9:S-325.
46. +-Glucuronidation of aliphatic tertiary amines in human: antidepressant versus antipsychotic drugs. Xenobiotica 25:291-301.
47. Luo H, Hawes EM, McKay G and Midha KK (1992b) Synthesis and characterization of quaternary ammonium-linked glucuronide metabolites of drugs with an aliphatic tertiary amine group. J Pharm Sci 81:1079-1083.
48. +-glucuronide in the urine of patients treated with clozapine using electrospray mass spectrometry. Biol Mass Spectrom 23:147-148.
49. MacRae PV, Kinns M, Pullen FS and Tarbit MH (1990) Characterization of a quaternary, N-glucuronide metabolite of the imidazole antifungal, tioconazole. Drug Metab Dispos 18: 1100-1102.
50. Magdalou J, Herber R, Bidault R and Siest G (1992) In vitro N-glucuronidation of a novel antiepileptic drug, lamotrigine, by human liver microsomes. J Pharmacol Exp Ther 260:1166-1173.
51. McKay G, Luo H, Hawes EM, Pidskalny N and Midha KK (1992) Electrospray ionization of quaternary ammonium-linked glucuronides and its comparison to mass spectra obtained by FAB. Proc Am Soc Mass Spectrom 40:1621-1622.
52. McKillop D, Pickup KJ, Swaisland AJ and Holmes BF (1990) The metabolic disposition of an orally active pyridyl thiadiazinone cardiotonic agent (MPTD) in rat and baboon. Xenobiotica 20:401-415.
53. 3H]econazole in man. Xenobiotica 11:595-608.
54. Nishikata M, Nikai A. Fushida H, Miyake K, Arita T, Iseki K, Miyazaki K and Nomura A (1993) Enantioselective pharmacokinetics of homochlorcyclizine III. Simultaneous determination of (+)-and (-)-homochlorcyclizine in human urine by high-performance liquid chromatography. J Chromatogr 612:239-244.
55. Nishikata M, Nomura A, Iseki K, Miyazaki K, Nikai A, Fushida H, Miyake K and Arita T (1992) Enantioselective pharmacokinetics of homochlorcyclizine II: Disposition and metabolism of (+)-, (-)-and racemic homochlorcyclizine after oral administration to man. Eur J Clin Pharmacol 43:533-538.
56. Parikh I, MacGlashan DW and Fenselau C (1976) Immobilized glucuronosyltransferase for the synthesis of conjugates. J Med Chem 19:296-299.
57. Perrier L, Bourrié M, Marti E, Tronquet C, Massé D, Berger Y, Magdalou J and Fahre G (1994) In vitro N-glucuronidation of SR 47436 (BMS 186295), a new AT1 nonpeptide angiotensin II receptor antagonist by rat, monkey and human hepatic microsomal fractions. J Pharmacol Exp Ther 271:91-99.
58. Porter CC, Arison BH, Gruber VF, Titus DC and Vandenheuvel WJA (1975) Human metabolism of cyproheptadine. Drug Metab Dispos 3:189-197.
59. Remmel RP and Sinz MW (1991) A quaternary ammonium glucuronide is the major metabolite of lamotrigine in guinea pigs: In vitro and in vivo studies. Drug Metab Dispos 19:630-636.
60. Rubin A, Dhahir PH, Crabtree RE and Henry DP (1979) The disposition of 1-3-[(dimethylamino)-(m-dioxan-5-yl)methyl]pyridine in man. Drug Metab Dispos 7:149-154.
61. Rush WR, Alexander OF, Hall DJ, Dow RJ, Tokes L, Kurz L and Graham DJM (1990) The metabolism of nafimidone hydrochloride in the dog, primates and man. Xenobiotica 20:123-132.
62. Rush WR, Hall DJ, Graham DJM and Selby IA (1992) The metabolism of imiloxan hydrochloride in healthy male volunteers. Xenobiotica 22:237-246.
63. Seaton MJ, Vesell ES, Luo H and Hawes EM (1993) Identification of radiolabeled metabolites of nicotine in rat bile. Synthesis of S-(-)nicotine N-glucuronide and direct separation of nicotine-derived conjugates using high-performance liquid chromatography. J Chromatogr 621:49-53.
64. Sharp S, Mak LY, Smith DJ and Coughtrie MWH (1992) Inhibition of human and rabbit liver steroid and xenobiotic UDP-glucuronosyltransferases by tertiary amine drugs-implications for adverse drug reactions. Xenobiotica 22:13-25.
65. Sinz MW and Remmel RP (1991a) Analysis of lamotrigine and lamotrigine 2N-glucuronide in guinea pig blood and urine by reversed-phase ion-pairing liquid chromatography. J Chromatogr 571:217-230.
66. Sinz MW and Remmel RP (1991b) Isolation and characterization of a novel quaternary ammonium-linked glucuronide of lamotrigine. Drug Metab Dispos 19:149-153.
67. Steams RA, Doss GA, Miller RR and Chiu S-HL (1991) Synthesis and identification of a novel tetrazole metabolite of the angiotensin II receptor antagonist DuP 753. Drug Metab Dispos 19:1160-1162.
68. Takeuchi M, Nakano M, Mizojiri K, Iwatani K, Nakagawa Y, Kikuchi J and Terui Y (1989) Quaternary ammonium glucuronide of croconazole in rabbits. Xenobiotica 19:1327-1336.
69. Williams DH and Fleming I (1987) Spectroscopic Methods in Organic Chemistry. 4th ed, pp 49, McGraw-Hill, London.