Metabolism of benzamidoxime (N-hydroxyamidine) in human hepatocytes and role of UDP-glucuronosyltransferases

Xenobiotica

Volumn 35, Issue 1, 2005, Pages 17-25

  Frohlich A K ^a   Girreser, U ^a   Clement, B ^a  

^a UNIVERSITY OF KIEL   (Germany)

Author keywords

Benzamidine; Benzamidoxime; Human hepatocyte culture; N hydroxyamidine; Pro drugs; UDP glucuronosyltransferases

Indexed keywords

AMIDINE; BENZAMIDOXIME; GLUCURONOSYLTRANSFERASE; PRODRUG; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; CRYOPRESERVATION; DRUG METABOLISM; ELECTROSPRAY; ENZYME METABOLISM; HUMAN; HUMAN CELL; LIQUID CHROMATOGRAPHY; LIVER CELL; MASS SPECTROMETRY; OXIDATION;

BENZAMIDINES; CELLS, CULTURED; GLUCURONOSYLTRANSFERASE; HEPATOCYTES; HUMANS; METABOLIC CLEARANCE RATE; OXIDATION-REDUCTION; PRODRUGS; RECOMBINANT PROTEINS;

SUS SCROFA;

EID: 16244387932     PISSN: 00498254     EISSN: None     Source Type: Journal    
DOI: 10.1080/00498250400021895     Document Type: Article

References (26)

1. Brandon EFA, Raap CD, Meijerman I, Beijnen JH, Schellens JHM. 2003. An update on in vitro test methods in human hepatic drug biotransformation research: pros and contras. Toxicology and Applied Pharmacology 15:233-246.
2. Clement B. 1983. The N-oxidation of benzamidines in vitro. Xenobiotica 13:467-473.
3. Clement B. 1993. Methoden zur Behandlung und Prophylaxe der Pneumocystis carinii Pneumonie (PCP) und anderen Erkrankungen sowie Verbindungen und Formulierungen zum Gebrauch bei besagten Methoden, Dt. Patentanmeldung (1993), P 4321444.4, PCT/DE 94/00756 (1994), Europe (0 708640, 16.09.1998), USA (5, 786, 383; 28.06.1998).
4. Clement B. 2002. Reduction of N-hydroxylated compounds: amidoximes (N-hydroxyamidines) as pro-drugs of amidines. Drug Metabolism Reviews 34:565-579.
5. Clement B, Lopian K. 2003. Characterization of in vitro biotransformation of new, orally active, direct thrombin inhibitor ximelagatran, an amidoxime and ester prodrug. Drug Metabolism and Disposition 31:645-651.
6. Clement B, Christiansen K, Girreser U. 2001. Phase 2 metabolites of N-hydroxylated amidines (amidoximes): synthesis, in vitro formation by pig hepatocytes, and mutagenicity testing. Chemical Research in Toxicology 14:319-326.
7. Clement B, Immel M, Schmitt S, Steinmann U. 1993. Biotransformation of benzamidine and benzamidoxime in vivo. Archiv der Pharmazie (Weinheim) 326:807-812.
8. Clement B, Schmitt S, Zimmermann M. 1988. Enzymatic reduction of benzamidoxime to benzamidine. Archiv der Pharmazie 321:955-956.
9. Fisher MB, Paine MF, Strelevitz TJ, Wrighton SA. 2001. The role of hepatic and extrahepatic UDP-glucuronosyltransferases in human drug metabolism. Drug Metabolism Reviews 33:273-297.
10. Hauptmann J, Paintz M, Kaiser B, Richter M. 1988. Reduction of a benzamidoxime derivative to the corresponding benzamidine in vivo and in vitro. Pharmazie 43:559-560.
11. Jurima-Romet M, Casley WL, Leblanc CA, Nowakowska M. 2000. Evidence for the catalysis of dextromethorphan O-demethylation by a CYP2D6-like enzyme in pig liver. Toxicology In Vitro 14:253-263.
12. LeCluyse EL. 2001. Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. European Journal of Pharmaceutical Sciences 13:343-368.
13. MacGregor JT, Collins JM, Sugiyama Y, Tyson CA, Denan J, Smith L, Andersen M, Curren RD, Hoeutson JB, Kadlubar F, Kedderis GL, Krishnan K, Li AP, Parchment RE, Thummel K, Tomaszewski JE, Ulrich R, Vickers AEM, Wrighton SA. 2001. In vitro human tissue models in risk assessment: report of a consensus-building workshop. Toxicological Sciences 59:17-36.
14. Mackenzie PI, Owens IS, Burchell B, Bock KW, Bairoch A, Bélanger A, Fournel-Gigleux S, Green M, Hum DW, Iyanagi T, Lancet D, Lousisot P, Magdalou J, Chowdhury JR, Ritter JK, Schachter H, Tephly TR, Tipton KF, Neben DW. 1997. The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence. Pharmacogenetics 7:255-269.
15. Mau S. 2002. Studien zur extrahepatischen Reduktion verschiedener N-hydroxylierter Verbindungen. PhD thesis.
16. Radominska-Pandya A, Czernik PJ, Little JM. 1999. Structural and functional studies of UDP-glucuronosyltransferases. Drug Metabolism Reviews 31:817-899.
17. Sheil AG. 2002. Xenogenetic bioartificial liver support: where are we now? Transplantation Proceedings 34:2493-2495.
18. Skaanild MT, Friis C. 1997. Characterization of the P450 system in Göttingen minipigs. Pharmacology and Toxicology 80(Suppl. 2):28-33.
19. Soucek P, Zuber R, Anzenbacherová E, Anzenbacher P, Guengerich FP. 2001. Minipig cytochrome P450 3A, 2A and 2C enzymes have similar properties to human analogs. BMC Pharmacology 1:11.
20. Strassburg CP, Strassburg A, Nguyen N, Li Q, Manns MP, Tukey RH. 1999. Regulation and function of family 1 and family 2 UDP-glucuronosyltransferase genes (UGT1A, UGT2B) in human oesophagus. The Biochemical Journal 338:489-498.
21. Tiemann F, Krüger P, 1885. Über Amidoxime und Azoxime. Berichte der Deutshen Chemischen Gesellschaft 18:1055-1060.
22. Tukey RH, Strassburg CP. 2000. Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annual Reviews of Pharmacology and Toxicology 40:581-616.
23. Weller T, Alig L, Beresini M, Blackburn B, Bunting S, Hadvary P, Muller MH, Knopp D, Levet-Trafit B, Lipari MT, Modi NB, Muller M, Refino CJ, Schmitt M, Schonholzer P, Weiss S, Steiner B. 1996. Orally active fibrinogen receptor antagonists. 2. Amidoximes as prodrugs of amidines. Journal of Medicinal Chemistry 39:3139-3147.
24. 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 Metabolism and Disposition 32:281-290.
25. Yueh M-F, Nguyen N, Famourzadeh M, Strassburg CP, Oda Y, Guengerich FP, Tukey RH. 2001. The contribution of UDP-glucuronosyltransferase 1A9 on CYP1A2-mediated genotoxicity by aromatic and heterocyclic amines. Carcinogenesis 22:943-950.
26. Zuber R, Anzenbacherova E, Anzenbacher P. 2002. Cytochromes P450 and experimental models of drug metabolism. Journal of Cellular and Molecular Medicine 6:189-198.