Biotransformation profiling of [14C]Ixabepilone in human plasma, urine and feces samples using accelerator mass spectrometry (AMS)

Drug Metabolism and Pharmacokinetics

Volumn 24, Issue 6, 2009, Pages 511-522

  Çömezoǧlu, S Nilgün ^a   Ly, Van T ^a   Zhang, Donglu ^a   Humphreys, W Griffith ^a   Bonacorsi, Samuel J ^a   Everett, Donald W ^a   Cohen, Marvin B ^a   Gan, Jinping ^a   Beumer, Jan H ^b   Beijnen, Jos H ^c   Schellens, Jan H M ^c   Lappin, Graham ^d  

^a BRISTOL MYERS SQUIBB   (United States)

^b UNIVERSITY OF PITTSBURGH CANCER INSTITUTE   (United States)

^c NETHERLANDS CANCER INSTITUTE   (Netherlands)

^d Xceleron Ltd   (United Kingdom)

Author keywords

Accelerator mass spectrometry (AMS); Human; Ixempra cancer; Metabolism; Metabolite; Xabepilone

Indexed keywords

IXABEPILONE C 14; RADIOPHARMACEUTICAL AGENT; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG FECES LEVEL; DRUG STRUCTURE; DRUG TRANSFORMATION; DRUG URINE LEVEL; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METABOLITE; OXIDATION; RADIOACTIVITY;

EID: 73349124146     PISSN: 13474367     EISSN: 18800920     Source Type: Journal    
DOI: 10.2133/dmpk.24.511     Document Type: Article

References (26)

1. Hoä fle, G., Bedorf, N., Steinmetz, H., Schemburg, D., Gerth, K. and Reicenbach, H.: Epothilone A and B - novel 16-membered macrolides and cytotoxic activity: isolation, crystal structure and conformation in solution. Angew. Chem. In. Ed. Eng., 35: 1567-1569 (1996).
2. Gerth, K., Bedorf, N., Häofle, G., Irschik, H. and Reichenbach, H.: Epothilones A and B: antifungal and cytotoxic compounds from Sorangium cellulosum (Myxobacteria). Production, physico- chemical and biological properties. J. of Antibiotics., 49: 560-563 (1996).
3. Bollag, D. M., McQueney, P. A., Zhu, J., Hensens, O., Koupal, L., Liesch, L., Goetz, M., Lazarides, E. and Woods, C. M.: Epothilones, a new class of microtubule-stabilizing agents with a Taxol-like mechanism of action. Cancer Res., 55: 2325-2333 (1995).
4. Bollag, D. M.: Epothilones: novel microtubule-stabilizing agents. Exp. Opin. Invest. Drugs., 6: 867-873 (1997).
5. Nettles, J., Li, H., Cornett, B., Krahn, J. M., Snyder, J. P. and Downing, K. H.: The binding mode of epothilone A on alpha, beta-tubulin by electron crystallography. Science., 305: 866-869 (2004).
6. Yamaguchi, H., Paranawithana, S. R., Lee, M. W., Huang, Z., Bhalla, K. N. and Wang, H.-G.: Epothilone B Analogue (BMS- 247550)-mediated Cytotoxicity through Induction of Bax Conformational Change in Human Breast Cancer Cells. Cancer Res., 62(2): 466-471 (2002).
7. Lee, F. Y. F., Borzilleri, R., Fairchild, C. R., Kim, S.-H., Long, B. H., Reventos-Suarez, C., Vite, G. D., Rose, W. C. and Kramer, R. A.: BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but processing superior antitumor efficacy. Clin. Cancer Res., 7: 1429-1437 (2001).
8. Bennet, C. L., Beukens, R. P., Glover, M. R., Gove, H. E., Liebert, R. B., Litherland, A. E., Purser, K. H. and Sondheim, W. E.: Radiocarbon dating using electrostatic accelerators: negative ions provide the key. Science, 198: 508-510 (1977).
9. Nelson, D. E., Korteling, R. G. and Stott, W. Y.: Carbon-14: direct detection at netural concentrations. Science, 198: 507-508 (1977).
10. Vogel, J. S., Turteltaub, K.W., Finkel, R. and Nelson, D. E.: Accelerator mass spectrometry - isotope quantification at attomole sensitivity. Anal. Chem., 67: 353A-359A (1995).
11. Garner, R. C.: Accelerator mass spectrometry in pharmaceutical research and development - a new ultrasensitive analytical method for isotope measurements. Curr. Drug Metab., 1: 205-213 (2000).
12. Kaye, B., Garner, R. C., Mauthe, R. J., Freeman, S. P. H. T. and Turteltaub, K. W.: A preliminary evaluation of accelerator mass spectrometry in the biomedical field. J. Pharm. Biomed. Anal., 16: 541-543 (1997).
13. Barker, J. and Garner, R. C.: Biomedical applications of accelerator mass spectrometry-Isotope measurements at the level of the atom. Rapid Commun. Mass Spectrom., 13: 285-293 (1999).
14. Garner, R. C., Goris, I., Laenen, A. A. E., Vanhoutte, E., Meuldermans, W., Gregory, S., Garner, J. V., Leong, D., Whattam, M., Calam, A. and Snel, C. A. W.: Evaluation of accelerator mass spectrometry in human mass balance and pharmacokinetic study-experience with 14C-labeled (R)-6-[amino(4-chlorophenyl) (1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)1-methyl-2 (1H)-quinolinone (R115777), a farnesyl transferase inhibitor. Drug Metab. Dispos., 30: 823-830 (2002).
15. Garner, R. C., Garner, J. V., Gregory, S., Whattam, M., Calam, A. and Leong, D.: Comparison of the absorption of micronized (Daflon 500 mg) and nonmicronized 14C-Diosmin tablets afteroral administration to healthy volunteers by accelerator mass spectrometry and liquid scintillation counting. J. Pharmaceutical Sciences., 91(1): 32-40 (2002).
16. Young, G., Ellis, W., Ayrton, J., Hussey, E. and Adamkiewicz, B.: Accelerator mass spectrometry (AMS): recent experience of its use in a clinical study and the potential future of the technique. Xenobiotica., 31(8/9): 619-632 (2001).
17. Brown, K., Tompkins, E. M. and White, I. N. H.: Applications of accelerator mass spectrometry for pharmaceutical and toxicological research. Mass Spect. Reviews., 25: 127-145 (2006).
18. Turteltaub, K. W. and Vogel, J. S.: Applications of accelerator mass spectrometry for pharmaceutical research. Current Pharm. Design., 6: 991-1007 (2000).
19. Turteltaub, K. W., Brown, K. and Dingley, K. H.: Accelerator mass spectrometry for biomedical research. Methods in Enzymology., 402: 423-443 (2005).
20. Miyaoka, T., Isono, Y., Setani, K., Sakai, K., Yamada, I., Sato, Y., Gunji, S. and Matsui, T.: Bioanalysis works in the IAA AMS facility: Comparison of AMS analytical method with LSC method in human mass balance study. Nuclear Instruments and Methods in Physics Research B., 259: 779-785 (2007).
21. Beumer, J. H., Garner, R. C., Cohen, M. B., Galbraith, S., Duncan, G. F., Griffin, T., Beijnen, J. H. and Schellens, J. H. M.: Human mass balance study of a novel anticancer agent ixabepilone using accelerator mass spectrometry. Invst. New Drugs., 25: 327-334 (2007).
22. Garner, R. C., Barker, J., Flavell, C., Garner, J. V., Whattam, M., Young, G. C., Cussans, N., Jezequel, S. and Leong, D.: A validation study comparing accelerator MS and liquid scintillation counting for analysis of 14C-labelled drugs in plasma, urine and fecal extracts. J. Pharm. Biomed. Anal., 24: 197-209 (2000).
23. Vogel, J. S.: Rapid production of graphite without contamination for biomedical AMS. Radiocarbon., 34: 344-350 (1992).
24. Lappin, G. and Garner, R. C.: Big physics, small doses: the use of AMS and PET in human microdosing of development drugs. Nature Reviews., 2: 233-240 (2003).
25. Turteltaub, K.W. and Dingley, K. H.: Application of accelerated spectrometry (AMS) in DNA adduct quantification and identification. Tox. Lett., 102-103: 435-439 (1998).
26. Goel, S., Cohen, M., Comezoglu, S. N., Perrin, L., Andre, F., Jayabalan, D., Iacono, L., Comprelli, A., Ly, V. T., Zhang, D., Xu, C., Humphreys, W. G., McDaid, H., Goldberg, G., Horwitz, S. and Mani, S.: The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of ixabepilone: A first in class epothilone B analogue in late-phase clinical development. Clin. Cancer Res., 14(9): 2701-2709 (2008).