Characterization of benzimidazole and other oxidative and conjugative metabolites of brimonidine in vitro and in rats in vivo using on-line H/D exchange LC-MS/MS and stable-isotope tracer techniques

Xenobiotica

Volumn 37, Issue 2, 2007, Pages 205-220

  Ni, J ^a   Rowe, J ^a   Heidelbaugh, T ^b   Sinha, S ^b   Acheampong, A ^a  

^a Department of Drug Safety Evaluation ^*  (United States)

^b ALLERGAN INC   (United States)

Author keywords

Aldehyde oxidase; Benzimidazole; Brimonidine; H D exchange; LC MS MS; Quinoxaline ring oxidation; Stable isotope tracer

Indexed keywords

BENZIMIDAZOLE; BRIMONIDINE; TRACER;

AEROBIC METABOLISM; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; HUMAN; HUMAN CELL; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; NONHUMAN; OXIDATION; RABBIT; RAT; STANDARDIZATION;

ADRENERGIC ALPHA-AGONISTS; ALDEHYDE OXIDASE; ANIMALS; BENZIMIDAZOLES; DEUTERIUM; HUMANS; HYDROGEN; MALE; MICROSOMES, LIVER; MODELS, BIOLOGICAL; QUINOXALINES; RABBITS; RATS; RATS, SPRAGUE-DAWLEY; TANDEM MASS SPECTROMETRY;

ORYCTOLAGUS CUNICULUS; RATTUS;

EID: 33847028035     PISSN: 00498254     EISSN: 13665928     Source Type: Journal    
DOI: 10.1080/00498250601047897     Document Type: Article

References (23)

1. Acheampong A, Chien D, Lam S, Cekich S, Breau A, Usansky J, Harcourt D, Munk S, Nguyen H, Garst M, et al. 1996. Characterization of brimonidine metabolism with rat, rabbit, dog, monkey and human liver fractions and rabbit liver aldehyde oxidase. Xenobiotica 26(10):1035-1055.
2. Acheampong A, Shackleton M, Tang-Liu D. 1995. Comparative ocular pharmacokinetics of brimonidine after a single dose application to the eyes of albino and pigmented rabbits. Drug Metabolism and Disposition 23(7):708-712.
3. Angelov O, Wiese A, Tang-Liu D, Acheampong A, Ismail I, Brar B. 1996. Preclinical safety profile of brimonidine. European Journal of Ophthalmology 6(1):21-25.
4. Baillie TA, Neill E, Hughes H, Davies DL, Davies DS. 1979. Application of stable isotope labeling in studies of the metabolism of clonidine in rat liver. In Klein RE, Klein PD, editors. International Conference In Proceeding of the 3rd International Conference on Stable Isotopes, New York: Academic, pp. 415-425.
5. Bailie TA, Rettenmeier AW. 1986. Recent Advances in the use of stable isotopes in drug metabolism research. Journal of Clinical Pharmacology 26:481-484.
6. Beedham C, Al-Tayib Y, Smith JA. 1992. Role of guinea pig and rabbit hepatic aldehyde oxidase in oxidative in vitro metabolism of cinchona antimalarials. Drug Metabolism and Disposition 20(6):889-95.
7. Damani LA, Crooks PA. 1982. Oxidative metabolism of heterocyclic rings. In: Jakoby WB, Bend JR, Caldwell J, editors. Metabolic basis of detoxification. New York: Academic. pp 69-90.
8. He M, Abraham TL, Lindsay TJ, Chay SH, Czeskis BA, Shipley LA. 2000. Metabolism and disposition of moxonidine in Fischer 344 rats. Drug Metabolism and Disposition 28(4):446-59.
9. He M, Abraham TL, Lindsay TJ, Schaefer HC, Pouliquen IJ, Payne C, Czeskis B, Shipley LA, Oliver SD, Mitchell MI. 2003. Metabolism and disposition of the antihypertensive agent moxonidine in humans. Drug Metabolism and Disposition 31(3):334-342.
10. Jeon YT, Gluchowski C, PCT US95/09895 (2003) and WO 96/04270 (1999).
11. Johnson C, Stubley C, Stell J. 1984. Elevation of molybdenum hydroxylase levels in rabbit liver after ingestion of phthalazine or its hydroxylated metabolite. Biochemical Pharmacology 33:3699-3705.
12. Leung LY, Baillie TA. 1989. Studies on the biotransformation of ketamine. II - quantitative significance of the N-demethylation pathway in rats in vivo determined by a novel stable isotope technique. Biomedical and Environmental Mass Spectrometry 18(6):401-404.
13. Liu DQ, Hop CECA. 2005. Strategies for characterization of drug metabolites using liquid chromatography-tandem mass spectrometry in conjunction with chemical derivatization and on-line H/D exchange approaches. Journal of Pharmaceutical and Biomedical Analysis 37(1):1-18.
14. Liu DQ, Hop CECA, Beconi MG, Mao A, Chiu SHL. 2001. Use of on-line hydrogen/deuterium exchange to facilitate metabolite identification. Rapid Communication of Mass Spectrometry 15:1832-39.
15. Ma S, Wwapan CK, Alton KB. 2006. Application of mass spectrometry for metabolite identification. Current Drug Metabolism 7:503-523.
16. Midgley I, Fowkes AG, Chasseaud LF, Hawkins DR, Girkin R. 1983. Biotransformation of lofexidine in humans. Xenobiotica 13(2):87-95.
17. Ohashi N, Furuuchi S, Yoshikawa M. 1998. Retention mechanism of imidazoles in connective tissue. IV. Identification of a nucleophilic imidazolone metabolite in rats. Journal of Pharmaceutical and Biomedical Analysis 18:325-34.
18. Schillings RT, Sisenwine S, Ruelius HW. 1977. Disposition and metabolism of lorazepam in the male rat. Drug Metabolism and Disposition 5(5):425-435.
19. Schulz-Jander DA, Casida JE. 2002. Imidacloprid insecticide metabolism: Human cyochrome P450 isozymes differ in selectivity for imidazolindine oxidation versus nitroimine reduction. Toxicology Letters 132:65-70.
20. Sisenwine SF, Tio CO. 1986. The metabolic disposition of oxazepam in rats. Drug Metabolism and Disposition 14(1):41-45.
21. Stubley C, Stell JGP, Mathieson DW. 1979. The oxidation of azaheterocycles with mammalian liver aldehyde oxidase. Xenobiotica 9:475-484.
22. Toris CB, Gleason ML, Camras CB, Yablonski ME. 1995. Effects of brimonidine on aqueous humor dynamics in human eyes. Archives of Ophthalmology 113:1514-1517.
23. Walters T. 1996. Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: A review of safety, efficacy, dose response and dosing studies. Survey of Ophthalmology 41:S19-26.