Biomedical accelerator mass spectrometry: Recent applications in metabolism and pharmacokinetics

Expert Opinion on Drug Metabolism and Toxicology

Volumn 4, Issue 8, 2008, Pages 1021-1033

  Lappin, Graham ^a   Stevens, Lloyd ^b  

^a Xceleron Ltd   (United Kingdom)

^b PHARMACEUTICAL PROFILES LTD   (United Kingdom)

Author keywords

Accelerator mass spectrometry; Drug metabolites; Intravenous pharmacokinetics

Indexed keywords

CARBON 14; DRUG; DRUG METABOLITE; ERYTHROMYCIN; EXCIPIENT; FEXOFENADINE; MELOXICAM; MIDAZOLAM; NELFINAVIR; TOLBUTAMIDE; TRACER; ZIDOVUDINE;

ACCELERATOR MASS SPECTROMETRY; AREA UNDER THE CURVE; CLINICAL TRIAL; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DESIGN; DRUG DETERMINATION; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG LABELING; DRUG METABOLISM; DRUG SAFETY; FOOD AND DRUG ADMINISTRATION; GOOD MANUFACTURING PRACTICE; HUMAN; INTERMETHOD COMPARISON; ISOTOPE LABELING; LOW DRUG DOSE; MASS SPECTROMETRY; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PHARMACOKINETICS; QUANTITATIVE ANALYSIS; RADIOSENSITIVITY; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; REVIEW;

BIOLOGICAL AVAILABILITY; CARBON RADIOISOTOPES; CLINICAL TRIALS, PHASE I AS TOPIC; DRUG DESIGN; GUIDELINES AS TOPIC; HUMANS; INJECTIONS, INTRAVENOUS; MASS SPECTROMETRY; PHARMACOKINETICS; TISSUE DISTRIBUTION; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 51049120013     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425255.4.8.1021     Document Type: Review

References (56)

1. Garner RC. Accelerator mass spectrometry in pharmaceutical research and development - a new ultrasensitive analytical method for isotope measurement. Curr Drug Metab 2000;1(2):205-13
2. Bennett CL, Beukens RP, Clover MR, et al. Purser, radiocarbon dating with electrostatic accelerators: dating of milligram samples. Science 1978;201(4353):345-7
3. Nelson DE, Korteling RG, Stott WR. Carbon-14: direct detection at natural concentrations. Science 1977;198:507-8
4. Salehpour M, Possnert G, Bryhni H. Zeptomole sensitivity in biological accelerator mass spectrometry. Anal Biochem 2008;80(10):3515-21
5. Lappin G, Garner RC. Ultra-sensitive detection of radiolabelled drugs and their metabolites using accelerator mass spectrometry. In: Wilson I, editor, Handbook of analytical separations. Elsevier: Amsterdam; 2003. p. 331-49
6. Lappin G. Garner RC. Current perspectives of 14C-isotope measurement in biomedical accelerator mass spectrometry. Anal Biochem 2004;378(2):356-64
7. Whitby B. Quantitative whole body autoradiography. In: Lappin G, Temple S, editors, Radiotracers in drug development. Taylor & Francis, CRC Press: Florida, USA; 2006
8. Beumer JH, Garner RC, Cohen MB, et al. Schellens, human mass balance study of the novel anticancer agent ixabepilone using accelerator mass spectrometry. Invest New Drugs 2007;25(4):327-34
9. Klem B, Lappin G, Nicholson S, et al. Determination of the bioavailability of [14C]-hexaminolevulinate using accelerator mass spectrometry after intravesical administration to human volunteers. J Clin Pharmacol 2006;46:456-60
10. Lappin G, Garner RC. The use of accelerator mass spectrometry to obtain early human ADME/PK data. Expert Opin Drug Metab Toxicol 2005;1(1):23-32
11. Turteltaub KW, Vogel JS. Bioanalytical applications of accelerator mass spectrometry for pharmaceutical research. Curr Pharm Des 2000;6(10):991-1007
12. Young G, Ellis W, Ayrton J, et al. Accelerator mass spectrometry (AMS): recent experience of its use in a clinical study and the potential future of the technique. Xenobiotica 2001;31(8-9):619-32
13. Young G, Ellis WJ. AMS in drug development at GSK. Nucl Instr Methods Phys Res 2007;B(259):752-7
14. Lappin G, Temple S. Radiotracers in drug development. Taylor & Francis, CRC Press; 2006
15. Lappin G, Garner RC. A review of human phase 0 and microdosing clinical trials following the US food and drug administration exploratory investigational new drug studies guidance. In J Pharm Med 2006;30(3):159-65
16. Garner RC, Lappin G. The phase 0 microdosing concept. Br J Clin Pharmacol 2006;61(4):367-70
17. EMEA, Position paper on non-clinical safety studies to support clinical trials with a single microdose. Position paper CPMP/SWP/2599; 23 June 2004
18. Food and Drug Administration US Department of Health and Human Services Guidance for Industry Investigators and Reviewers. Exploratory IND Studies. January 2006
19. Combes RD, Berridge T, Connelly J, et al. Early microdose drug studies in human volunteers can minimise animal testing: Proceedings of a workshop organised by Volunteers in Research and Testing. Eur J Pharm Sci 2003;19(1):1-11
20. Wagner CC, Muller M, Lappin G, Langer O. Positron emission tomography for use in microdasing studies. Curr Opin Drug Discov Devel 2008;11(1):104-10
21. Garner RC. Less is more: the human microdosing concept. Drug Discov Today 2005;10(7):449-51
22. Buchan P. Smarter candidate selection - utilizing microdosing in exploratory clinical studies. Ernst Schering Res Found Workshop 2007;59:7-27
23. Zanni GR, Wick JY. Microdosing: the new pharmacokinetic paradigm? Consult Pharm 2006;21(10):756-76
24. Garner RC. Less is more the human microdosing concept. Drug Discov Today 2005:449-51
25. Sudo K. Microdosing for reduction of the time and resource for drug development. Drug Metab Pharmacokinet 2007;22(5):327
26. Marchetti S, Schellens JHM. The impact of FDA and EMEA guidelines on drug development in relation to phase 0 trials. Br J Cancer 2007;97:577-81
27. Sparreboom A. Unexplored pharmacokinetic opportunities with microdosing in oncology. Clin Cancer Res 2007;13(14):4033-4
28. Robinson WT. Innovative early development regulatory approaches: expIND, expCTA, microdosing. Clin Pharmacol Ther 2008;83(2):358-60
29. Bauer M, Wagner CC, Langer O. Microdosing studies in humans: the role of positron emission tomography. Drugs R D 2008;9(2):73-81
30. Marchetti S, Schellens JH. The impact of FDA and EMEA guidelines on drug development in relation to Phase 0 trials. Br J Cancer 2007;97(5):577-81
31. Sudo K. Microdosing for reduction of the time and resources for drug development. Drug Metab Pharmacokinet 2007;22(5):327
32. Balani SK, Nagaraja NV, Qian MG, et al. Evaluation of microdosing to assess pharmacokinetic linearity in rats using liquid chromatography-tandem mass spectrometry. Drug Metab Dispos 2006;34(3):384-8
33. Lappin G, Kuhnz W, Jochemsen R, et al. Use of microdosing to predict pharmacokinetics at the therapeutic dose: experience with 5 drugs. Clin Pharmacol Ther 2006;80(3):203-15
34. Yamane N, Tozuka Z, Sugiyama Y, et al. Microdose clinical trial: quantitative determination of fexofenadine in human plasma using liquid chromatography/electrospray ionization tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2007;858(1-2):118-28
35. Ni J, Ouyang H, Aiello M, et al. Microdosing assessment to evaluate pharmacokinetics and drug metabolism in rats using liquid chromatography-tandem mass spectrometry. Pharm Res 2008;25(7):1572-82
36. Boyd RA, Lalonde RL. Nontraditional approaches to first-in-human studies to increase efficiency of drug development: will microdose studies make a significant impact? Clin Pharmacol Ther 2007;81(1):24-6
37. Rowland M. Commentary on ACCP position statement on the use of microdosing in the drug development process. J Clin Pharmacol 2007;47(12):1595-6; author reply 1597-8
38. Ndovi TT, Cao YJ, Fuchs E, et al. Food affects zidovudine concentration independent of effects on gastrointestinal absorption. J Clin Pharmacol 2007;47(11):1366-73
39. Lappin G, Rowland M, Garner RC. The use of isotopes in the determination of absolute bioavailability of drugs in humans. Expert Opin Drug Metab Toxicol 2006;2(3):419-27
40. Wong BK, Bruhin PJ, Lin JH. Dose-dependent plasma clearance of MK-826, a carbapenem antibiotic, arising from concentration-dependent plasma protein binding in rats and monkeys. J Pharm Sci 1999;88(2):277-80
41. Browne TR. Stable isotopes in clinical pharmacokinetic investigations. Advantages and disadvantages. Clin Pharmacokinet 1990;18(6):423-33
42. Rubin GM, Waschek JA, Pond SM, et al. Concurrent intravenous administration of a labeled tracer to determine the oral bioavailability of a drug exhibiting Michaelis-Menten metabolism. J Pharmacokinet Biopharm 1987;15(6):615-31
43. Lima JJ, Haughey DB, Leier CV. Disopyramide pharmacokinetics and bioavailability following the simultaneous administration of disopyramide and 14C-disopyramide. J Pharmacokinet Biopharm 1984;12(3):289-313
44. Sarapa N, Hsyu PH, Lappin G, Garner RC. The application of accelerator mass spectrometry to absolute bioavailability studies in humans: simultaneous administration of an intravenous microdose of 14C-nelfinavir mesylate solution and oral nelfinavir to healthy volunteers. J Clin Pharmacol 2005;45(10):1198-205
45. European Microdosing AMS Parnership Programme. Linear pharmacokinetics demonstrated between a microdose and therapeutic dose of the Pgp substrate fexofenadine in humans, in American Society for Clinical Pharmacology and Therapeutics. Florida, USA; 2008
46. Tahara H, Kusuhara H, Fuse E, Sugiyama Y. P-glycoprotein plays a major role in the efflux of fexofenadine in the small intestine and blood-brain barrier, but only a limited role in its biliary excretion. Drug Metab Dispos 2005;33(7):963-8
47. Shimizu M, Fuse K, Okudaira K, et al. Contribution of OATP (organic anion-transporting polypeptide) family transporters to the hepatic uptake of fexofenadine in humans. Drug Metab Dispos 2005;33(10):1477-81
48. Walker DK. The use of pharmacokinetic and pharmacodynamic data in the assessment of drug safety in early drug development. Br J Clin Pharmacol 2004;58(6):601-8
49. Liberman R, Skipper PL, Prakash C, et al. BEAMS Lab: novel approaches to finding a balance between throughput and sensitivity. Nucl Instr Methods Phys Res 2007;259:773-83
50. Liberman RG, Tannenbaum SR, Hughey BJ, et al. An interface for direct analysis of 14;c in nonvolatile samples by accelerator mass spectrometry. Anal Chem 2004;76(2):328-34
51. Lappin G, Simpson M, Shishikura Y, Garner C. High-performance liquid chromatography accelerator mass spectrometry: correcting for losses during analysis by internal standardization. Anal Biochem 2008;378:93-5
52. Food and Drug Administration US Department of Health and Human Services Guidance for Industry Safety Testing of Drug Metabolites, February 2008
53. Miller AK, Adir J, Vestal RE. Excretion of tolbutamide metabalites in young and old subjects. Eur J Clin Pharmacol 1990;38(5):523-4
54. Bateman KP, Castro-Perez J, Wrona M, et al. MSE with mass defect filtering for in vitro and in vivo metabolite identification. Rapid Commun Mass Spectrom 2007;21(9):1485-96
55. Waldmeier F, Garner C. Application of AMS for Human ADME. Drug Metab Rev 2001;33(1):121
56. Schmid J, Busch U, Trummlitz G, et al. Meloxicam: metabolic profile and biotransformation products in the rat. Xenobiotica 1995;25(11):1219-36