Use of radiolabeled compounds in drug metabolism and pharmacokinetic studies

Chemical Research in Toxicology

Volumn 25, Issue 3, 2012, Pages 532-542

  Isin, Emre M ^a   Elmore, Charles S ^a   Nilsson, Goiran N ^a   Thompson, Richard A ^a   Weidolf, Lars ^a  

^a ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON 14; DRUG METABOLITE; ESOMEPRAZOLE; IBUPROFEN; OMEPRAZOLE; TRITIUM; VERAPAMIL;

COVALENT BOND; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG METABOLISM; DRUG SAFETY; HUMAN; ISOTOPE LABELING; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; NONHUMAN; PHASE 3 CLINICAL TRIAL (TOPIC); REVIEW; WHOLE BODY AUTORADIOGRAPHY;

ANIMALS; CARBON RADIOISOTOPES; DRUG DISCOVERY; HUMANS; PHARMACEUTICAL PREPARATIONS; PHARMACOKINETICS; TRITIUM;

ANIMALIA;

EID: 84863393130     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/tx2005212     Document Type: Review

References (62)

1. Bateman, K. P., Castro-Perez, J., Wrona, M., Shockcor, J. P., Yu, K., Oballa, R., and Nicoll-Griffith, D. A. (2007) MSE with mass defect filtering for in vitro and in vivo metabolite identification. Rapid Commun. Mass Spectrom. 21, 1485-1496. (Pubitemid 46761970)
2. Mortishire-Smith, R. J., O'Connor, D., Castro-Perez, J. M., and Kirby, J. (2005) Accelerated throughput metabolic route screening in early drug discovery using high-resolution liquid chromatography/quadrupole time-of-flight mass spectrometry and automated data analysis. Rapid Commun. Mass Spectrom. 19, 2659-2670. (Pubitemid 41338609)
3. Bonn, B., Leandersson, C., Fontaine, F., and Zamora, I. (2010) Enhanced metabolite identification with MSE and a semi-automated software for structural elucidation. Rapid Commun. Mass Spectrom. 24, 3127-3138.
4. Castro-Perez, J. M. (2007) Current and future trends in the application of HPLC-MS to metabolite-identification studies. Drug Discovery Today 12, 249-256.
5. Tiller, P. R., Yu, S., Castro-Perez, J., Fillgrove, K. L., and Baillie, T. A. (2008) High-throughput, accurate mass liquid chromatography/tandem mass spectrometry on a quadrupole time-of-flight system as a 'first-line' approach for metabolite identification studies. Rapid Commun. Mass Spectrom. 22, 1053-1061. (Pubitemid 351468262)
6. Plumb, R. S., Mather, J., Little, D., Rainville, P. D., Twohig, M., Harland, G., Kenny, D. J., Nicholson, J. K., Wilson, I. D., and Kass, I. J. (2010) A novel LC-MS approach for the detection of metabolites in DMPK studies. Bioanalysis 2, 1767-1778.
7. Li, A. C., Ding, J., Jiang, X., and Denissen, J. (2009) Twoinjection workflow for a liquid chromatography/LTQ-Orbitrap system to complete in vivo biotransformation characterization: demonstration with buspirone metabolite identification. Rapid Commun. Mass Spectrom. 23, 3003-3012.
8. Guengerich, F. P. (2008) Oxidative, Reductive, and Hydrolytic Metabolism of Drugs, in Drug Metabolism in Drug Design and Development (Zhang, D., Zhu, M., and Humphreys, W. G., Eds.) pp 15-35, John Wiley & Sons, Hoboken, NJ.
9. Isin, E. M., and Guengerich, F. P. (2007) Complex reactions catalyzed by cytochrome P450 enzymes. Biochim. Biophys. Acta 1770, 314-329. (Pubitemid 46157073)
10. Guengerich, F. P. (2007) Mechanisms of cytochrome P 450 substrate oxidation. J. Biochem. Mol. Toxicol. 21, 163-168.
11. Northrop, D. B. (1975) Steady-state analysis of kinetic isotope effects in enzymic reactions. Biochemistry 14, 2644-2651.
12. Northrop, D. B. (1982) Deuterium and tritium kinetic isotope effects on initial rates. Methods Enzymol. 87, 607-625.
13. Krauser, J. A., and Guengerich, F. P. (2005) Cytochrome P450 3A4-catalyzed testosterone 6beta-hydroxylation stereochemistry, kinetic deuterium isotope effects, and rate-limiting steps. J. Biol. Chem. 280, 19496-19506. (Pubitemid 41379470)
14. Sanderson, K. (2009) Big interest in heavy drugs. Nature 458, 269.
15. Shao, L., and Hewitt, M. C. (2010) The kinetic isotope effect in the search for deuterated drugs. Drug News Perspect. 23, 398-404.
16. Malmlof, T., Rylander, D., Alken, R. G., Schneider, F., Svensson, T. H., Cenci, M. A., and Schilstrom, B. (2010) Deuterium substitutions in the L-DOPA molecule improve its anti-akinetic potency without increasing dyskinesias. Exp. Neurol. 225, 408-415.
17. Elmore, C. S. (2009) The use of isotopically labeled compounds in drug discovery. Annu. Rep. Med. Chem. 44, 515-534.
18. Voges, R., Hey, J. R., and Moenius, T. (2009) In Preparation of Compounds Labeled with Tritium and Carbon-14, John Wiley and Sons Ltd., Chichester, U.K.
19. Heys, J. R. (2007) Organoiridium complexes for hydrogen isotope exchange labeling. J. Labelled Compd. Radiopharm. 50, 770-778.
20. Hesk, D., Das, P. R., and Evans, B. (1995) Deuteration of acetanilides and other substituted aromatics using [Ir(COD)(Cy3P)-(Py)]PF6 as catalyst. J. Labelled Compd. Radiopharm. 36, 497-502.
21. Powell, M. E., Elmore, C. S., Dorff, P. N., and Heys, J. R. (2007) Investigation of isotopic exchange reactions using N-heterocyclic iridium (I) complexes. J. Labelled Compd. Radiopharm. 50, 523-525. (Pubitemid 47309079)
22. Nilsson, G. N., and Kerr, W. J. (2010) The development and use of novel iridium complexes as catalysts for ortho-directed hydrogen isotope exchange reactions. J. Labelled Compd. Radiopharm. 53, 662-667.
23. Saljoughian, M., and Williams, P. G. (2000) Recent developments in tritium incorporation for radiotracer studies. Curr. Pharm. Des. 6, 1029-1056. (Pubitemid 30439024)
24. Miller, J. A., and Miller, E. C. (1947) The metabolism and carcinogenicity of p-dimethylaminoazobenzene and related compounds in the rat. Cancer Res. 7, 39-41, also in Am. Assoc. Advance. Sci., Sect. on Chemistry, Gibson Island Research Conference on Cance,r 1946.
25. Miller, J. A., Sapp, R. W., and Miller, E. C. (1948) Absorption spectra of certain carcinogenic aminoazo dyes and the protein-bound derivatives formed from these dyes in vivo. J. Am. Chem. Soc. 70, 3458-3463.
26. Ju, C., and Uetrecht, J. P. (2002) Mechanism of idiosyncratic drug reactions: reactive metabolite formation, protein binding and the regulation of the immune system. Curr. Drug Metab. 3, 367-377. (Pubitemid 34778003)
27. Uetrecht, J. (2008) Idiosyncratic drug reactions: past, present, and future. Chem. Res. Toxicol. 21, 84-92.
28. Evans, D. C., and Baillie, T. A. (2005) Minimizing the potential for metabolic activation as an integral part of drug design. Curr. Opin. Drug Discovery Dev. 8, 44-50. (Pubitemid 40116329)
29. Evans, D. C., Watt, A. P., Nicoll-Griffith, D. A., and Baillie, T. A. (2004) Drug-protein adducts: an industry perspective on minimizing the potential for drug bioactivation in drug discovery and development. Chem. Res. Toxicol. 17, 3-16. (Pubitemid 38134055)
30. Nakayama, S., Atsumi, R., Takakusa, H., Kobayashi, Y., Kurihara, A., Nagai, Y., Nakai, D., and Okazaki, O. (2009) A zone classification system for risk assessment of idiosyncratic drug toxicity using daily dose and covalent binding. Drug Metab. Dispos. 37, 1970-1977.
31. Usui, T., Mise, M., Hashizume, T., Yabuki, M., and Komuro, S. (2009) Evaluation of the potential for drug-induced liver injury based on in vitro covalent binding to human liver proteins. Drug Metab. Dispos. 37, 2383-2392.
32. Obach, R. S., Kalgutkar, A. S., Soglia, J. R., and Zhao, S. X. (2008) Can in vitro metabolism-dependent covalent binding data in liver microsomes distinguish hepatotoxic from nonhepatotoxic drugs? An analysis of 18 drugs with consideration of intrinsic clearance and daily dose. Chem. Res. Toxicol. 21, 1814-1822.
33. Bauman, J. N., Kelly, J. M., Tripathy, S., Zhao, S. X., Lam, W. W., Kalgutkar, A. S., and Obach, R. S. (2009) Can in vitro metabolism-dependent covalent binding data distinguish hepatotoxic from nonhepatotoxic drugs? An analysis using human hepatocytes and liver S-9 fraction. Chem. Res. Toxicol. 22, 332-340.
34. Thompson, R. A., Isin, E. M., Li, Y., Weaver, R., Weidolf, L., Wilson, I., Claesson, A., Page, K., Dolgos, H., and Kenna, J. G. (2011) Risk assessment and mitigation strategies for reactive metabolites in drug discovery and development. Chem.-Biol. Interact. 192, 65-71.
35. Day, S. H., Mao, A., White, R., Schulz-Utermoehl, T., Miller, R., and Beconi, M. G. (2005) A semi-automated method for measuring the potential for protein covalent binding in drug discovery. J. Pharmacol. Toxicol. Methods 52, 278-285. (Pubitemid 41207205)
36. Plowright, A. T., Johnstone, C., Kihlberg, J., Pettersson, J., Robb, G., and Thompson, R. A. (2012) Hypothesis driven drug design: improving quality and effectiveness of the design-make-test-analyse cycle. Drug Discovery. Today 17, 56-62.
37. Busse, D., Cosme, J., Beaune, P., Kroemer, H. K., and Eichelbaum, M. (1995) Cytochromes of the P450 3C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn-Schmiedeberg's Arch. Pharmacol. 353, 116-121. (Pubitemid 26009826)
38. Kroemer, H. K., Gautier, J. C., Beaune, P., Henderson, C., Wolf, C. R., and Eichelbaum, M. (1993) Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn-Schmiedeberg's Arch. Pharmacol. 348, 332-337. (Pubitemid 23271638)
39. Eichelbaum, M., Ende, M., Remberg, G., Schomerus, M., and Dengler, H. J. (1979) The metabolism of DL-[14C]verapamil in man. Drug Metab. Dispos. 7, 145-148.
40. Ullberg, S. (1954) Autoradiographic distribution and excretion studies with sulfur35-labeled penicillin. Proc. Soc. Exp. Biol. Med. 85, 550-553.
41. Solon, E. G., Balani, S. K., and Lee, F. W. (2002) Whole-body autoradiography in drug discovery. Curr. Drug Metab. 3, 451-462. (Pubitemid 34982179)
42. Ullberg, S. (1954) Studies on the distribution and fate of S35-labelled benzylpenicillin in the body. Acta Radiol Suppl 118, 1-110.
43. Solon, E. G., Schweitzer, A., Stoeckli, M., and Prideaux, B. (2010) Autoradiography, MALDI-MS, and SIMS-MS imaging in pharmaceutical discovery and development. AAPS J. 12, 11-26.
44. Parson, W. B., and Caprioli, R. M. (2011) Profiling and Imaging of Tissues by Imaging Ion Mobility-Mass Spectrometry, in Ion Mobility Spectrometry-Mass Spectrometry (Wilkins, C. L., and Trimpin, S., Eds.) pp 269-286, CRC Press, New York.
45. Greer, T., Sturm, R., and Li, L. (2011) Mass spectrometry imaging for drugs and metabolites. J. Proteomics 74, 2617-2631.
46. Weidolf, L., Karlsson, K. E., and Nilsson, I. (1992) A metabolic route of omeprazole involving conjugation with glutathione identified in the rat. Drug Metab. Dispos. 20, 262-267.
47. Duncombe, W. G., and Rising, T. J. (1968) Biosynthesis of cyclopropyl long-chain fatty acids from cyclopropanecarboxylic acid by mammalian tissues in vitro. Biochem. J. 109, 449-455.
48. Quistad, G. B., Staiger, L. E., and Schooley, D. A. (1978) Environmental degradation of the miticide cycloprate (hexadecyl cyclopropanecarboxylate). 4. Beagle dog metabolism. J. Agric. Food Chem. 26, 76-80. (Pubitemid 8284765)
49. Dooley, G. P., Prenni, J. E., Prentiss, P. L., Cranmer, B. K., Andersen, M. E., and Tessari, J. D. (2006) Identification of a novel hemoglobin adduct in Sprague Dawley rats exposed to atrazine. Chem. Res. Toxicol. 19, 692-700. (Pubitemid 43800986)
50. Hamboeck, H., Fischer, R. W., Di Iorio, E. E., and Winterhalter, K. H. (1981) The binding of s-triazine metabolites to rodent hemoglobins appears irrelevant to other species. Mol. Pharmacol. 20, 579-584. (Pubitemid 12252279)
51. Guengerich, F. P. (2009) Introduction: Human Metabolites in Safety Testing (MIST) Issue. Chem. Res. Toxicol. 22, 237-238.
52. Food and Drug Administration (2008) Guidance for Industry Safety Testing of Metabolites, http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/ucm079266. pdf (accessed Nov 30, 2011).
53. European Medicines Agency (2009) ICH Topic M3 (R2): Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals, http://www.ema. europa.eu/docs/en-GB/document-library/ Scientific-guideline/2009/09/WC500002720.pdf (accessed Nov 30, 2011).
54. Yi, P., and Luffer-Atlas, D. (2010) A radiocalibration method with pseudo internal standard to estimate circulating metabolite concentrations. Bioanalysis 2, 1195-1210.
55. Zhang, D., Raghavan, N., Chando, T., Gambardella, J., Fu, Y., Zhang, D., Unger, S. E., and Humphreys, W. G. (2007) LC-MS/MS-based approach for obtaining exposure estimates of metabolites in early clinical trials using radioactive metabolites as reference standards. Drug Metab. Lett. 1, 293-298.
56. Ma, S., and Chowdhury, S. K. (2011) Analytical strategies for assessment of human metabolites in preclinical safety testing. Anal. Chem. 83, 5028-5036.
57. Ma, S., Li, Z., Lee, K., and Chowdhury, S. K. (2010) Determination of exposure multiples of human metabolites for MIST assessment in preclinical safety species without using reference standards or radiolabeled compounds. Chem. Res. Toxicol. 23, 1871-1873.
58. Gao, H., and Obach, R. S. (2011) Addressing MIST (Metabolites in Safety Testing): bioanalytical approaches to address metabolite exposures in humans and animals. Curr. Drug Metab. 12, 578-586.
59. Gao, H., Deng, S., and Obach, R. S. (2010) A simple liquid chromatography-tandem mass spectrometry method to determine relative plasma exposures of drug metabolites across species for metabolite safety assessments. Drug Metab. Dispos. 38, 2147-2156.
60. Hamilton, R. A., Garnett, W. R., and Kline, B. J. (1981) Determination of mean valproic acid serum level by assay of a single pooled sample. Clin. Pharmacol. Ther. 29, 408-413. (Pubitemid 11134120)
61. Nedderman, A. N., Dear, G. J., North, S., Obach, R. S., and Higton, D. (2011) From definition to implementation: a cross-industry perspective of past, current and future MIST strategies. Xenobiotica 41, 605-622.
62. Obach, R. S., Nedderman, A. N., and Smith, D. A. (2012) Radiolabelled mass-balance excretion and metabolism studies in laboratory animals: are they still necessary? Xenobiotica 42, 46-56.