A combined accelerator mass spectrometry-positron emission tomography human microdose study with 14C- and 11C-labelled verapamil

Clinical Pharmacokinetics

Volumn 50, Issue 2, 2011, Pages 111-120

  Wagner, Claudia C ^a   Simpson, Marie ^b   Zeitlinger, Markus ^a   Bauer, Martin ^a   Karch, Rudolf ^a   Abrahim, Aiman ^a   Feurstein, Thomas ^a   Schütz, Matthias ^a   Kletter, Kurt ^a   Müller, Markus ^a   Lappin, Graham ^b   Langer, Oliver ^a,c  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b Xceleron Ltd   (United Kingdom)

^c AIT AUSTRIAN INSTITUTE OF TECHNOLOGY   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON 11; CARBON 14; VERAPAMIL;

ACCELERATOR MASS SPECTROMETRY; ADULT; AREA UNDER THE CURVE; ARTICLE; BLOOD BRAIN BARRIER; BRAIN; CROSSOVER PROCEDURE; DISTRIBUTION VOLUME; DIZZINESS; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; ENANTIOMER; HUMAN; HUMAN EXPERIMENT; ISOTOPE LABELING; MALE; MASS SPECTROMETRY; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PLASMA; PLASMA CONCENTRATION-TIME CURVE; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RADIOACTIVITY; RANDOMIZED CONTROLLED TRIAL; STEADY STATE; TISSUE DISTRIBUTION;

AREA UNDER CURVE; BLOOD-BRAIN BARRIER; CALCIUM CHANNEL BLOCKERS; CARBON RADIOISOTOPES; CLINICAL TRIALS, PHASE I AS TOPIC; HALF-LIFE; HUMANS; MALE; MODELS, BIOLOGICAL; POSITRON-EMISSION TOMOGRAPHY; TANDEM MASS SPECTROMETRY; VERAPAMIL;

EID: 78751507504     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.2165/11537250-000000000-00000     Document Type: Article

References (44)

1. Committee for Medicinal Products for Human Use, European Medicines Agency. Position paper on non-clinical safety studies to support clinical trials with a single microdose [document reference CPMP/SWP/2599/02]. London: European Medicines Agency, 2004.
2. Center for Drug Evaluation and Research, US FDA. Guidance for industry, investigators, and reviewers: exploratory IND studies. Rockville (MD): FDA, 2006.
3. Graul AI. Promoting, improving and accelerating the drug development and approval processes. Drug News Perspect 2009; 22: 30-8.
4. Bertino Jr JS, Greenberg HE, Reed MD. American College of Clinical Phar- macology position statement on the use of microdosing in the drug development process. J Clin Pharmacol 2007; 47: 418-22.
5. 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: 203-15.
6. Madan A, O'Brien Z, Wen J, et al. A pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects. Br J Clin Pharmacol 2009; 67: 288-98.
7. Vuong T, Kopek N, Ducruet T, et al. Conformal therapy improves the ther- apeutic index of patients with anal canal cancer treated with combined chemotherapy and external beam radiotherapy. Int J Radiat Oncol Biol Phys 2007; 67: 1394-400.
8. Yamane N, Tozuka Z, Sugiyama Y, et al. Microdose clinical trial: quanti- tative determination of fexofenadine in human plasma using liquid chromatography/electrospray ionization tandem mass spectrometry. J Chro-matogr B 2007; 858: 118-28.
9. Lappin G, Garner RC. The utility of microdosing over the past 5 years. Expert Opin Drug Metab Toxicol 2008; 4: 1499-506.
10. Lappin G, Wagner CC, Langer O, et al. New ultra-sensitive detection tech- nologies and techniques for use in microdosing studies. Bioanalysis 2009; 1: 357-66.
11. Lappin G, Garner RC. The useof accelerator mass spectrometry to obtain early human ADME/PK data. Expert Opin Drug Metab Toxicol 2005; 1: 23-31.
12. Lappin G, Stevens L. Biomedical accelerator mass spectrometry: recent applications in metabolism and pharmacokinetics. Expert Opin Drug Metab Toxicol 2008; 4: 1021-33.
13. Muller M, de la Pena A, Derendorf H. Issues in pharmacokinetics and pharmacodynamics of anti-infective agents: II. Tissue distribution. Antimi-crob Agents Chemother 2004; 48: 1441-53.
14. Bergstrom M, Grahnen A, Langstrom B. Positron emission tomography microdosing: a new concept with application in tracer and early clinical drug development. Eur J Clin Pharmacol 2003; 59: 357-66.
15. Wagner CC, Muller M, Lappin G, et al. Positron emission tomography for use in microdosing studies. Curr Opin Drug Discov Devel 2008; 11: 104-10.
16. McTavish D, Sorkin EM. Verapamil: an updated review of its pharmacody- namic and pharmacokinetic properties, and therapeutic use in hypertension. Drugs 1989; 38: 19-76.
17. Brunner M, Langer O, Sunder-Plassmann R, et al. Influence of functional haplotypes in the drug transporter gene ABCB1 on central nervous system drug distribution in humans. Clin Pharmacol Ther 2005; 78: 182-90.
18. 14C-labeled R- and S-verapamil in plasma. Bioanalysis 2010; 2 (3): 397-405.
19. Robb RA. The biomedical imaging resource at Mayo Clinic. IEEE Trans Med Imaging 2001; 20: 854-67
20. Ashburner J, Friston KJ. Unified segmentation. Neuroimage 2005; 26: 839-51
21. 11C]verapamil. Epilepsia 2007; 48: 1774-84.
22. Hammers A, Allom R, Koepp MJ, et al. Three-dimensional maximum proba- bility atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp 2003; 19: 224-47.
23. 11C]verapamil in epilepsy patients. Eur J Nucl Med Mol Imaging 2008; 35: 116-23.
24. 11C]verapamil and PET. J Cereb Blood Flow Metab 2007; 27: 424-33.
25. 11C-methyl]-(-)-cocaine PET studies in human subjects. J Cereb Blood Flow Metab 1990; 10: 740-7.
26. LappinG, Rowland M, Garner RC. The use ofisotopes inthe determination of absolute bioavailability of drugs in humans. Expert Opin Drug Metab Tox-icol 2006; 2: 419-27.
27. Rubin GM, Waschek JA, Pond SM, et al. Concurrent intravenous adminis- tration of a labeled tracer to determine the oral bioavailability of a drug exhibiting Michaelis-Menten metabolism. J Pharmacokinet Biopharm 1987; 15: 615-31.
28. Dadashzadeh S, Javadian B, Sadeghian S. The effect of gender on the pharmacokinetics of verapamil and norverapamil in human. Biopharm Drug Dispos 2006; 27: 329-34.
29. 11C]verapamil as PET tracer of P-glycoprotein function in the blood-brain barrier: kinetics and metabolism in the rat. Nucl Med Biol 2005; 32: 87-93.
30. Pauli-Magnus C, von Richter O, Burk O, et al. Characterization of the major metabolites of verapamil as substrates and inhibitors of P-glycoprotein. J Pharmacol Exp Ther 2000; 293: 376-82
31. 14C]verapamil. J Med Chem 1971; 14: 1178-84
32. Eichelbaum M, Mikus G, Vogelgesang B. Pharmacokinetics of (+)-, (-)- and (+/-)-verapamil after intravenous administration. Br J Clin Pharmacol 1984; 17: 453-8.
33. Saleem A, Aboagye EO, Matthews JC, et al. Plasma pharmacokinetic evaluation of cytotoxic agents radiolabelled with positron emitting radio-isotopes. Cancer Chemother Pharmacol 2008; 61: 865-73.
34. Bergstrom M, Yates R, Wall A, et al. Blood-brain barrier penetration of zol- mitriptan-modeling of positron emission tomography data. J Pharmacokinet Pharmacodyn 2006; 33: 75-91.
35. Toffoli G, Robieux I, Fantin D, et al. Non-linear pharmacokinetics of high- dose intravenous verapamil. Br J Clin Pharmacol 1997; 44: 255-60.
36. Ambudkar SV, Dey S, Hrycyna CA, et al. Biochemical, cellular, and phar- macological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol 1999; 39: 361-98.
37. Wagner CC, Bauer M, Karch R, et al. A pilot study to assess the efficacy of tariquidar to inhibit P-glycoprotein at the human blood-brain barrier with (R)-11C-verapamil and PET. J Nucl Med 2009; 50: 1954-61.
38. Loscher W, Potschka H. Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases. Prog Neurobiol 2005; 76: 22-76.
39. Brandt C, Bethmann K, Gastens AM, et al. The multidrug transporter hypo- thesis of drug resistance in epilepsy: proof-of-principle in a rat model of temporal lobe epilepsy. Neurobiol Dis 2006; 24: 202-11.
40. Sisodiya SM, Bates SE. Treatment of drug resistance in epilepsy: one step at a time. Lancet Neurol 2006; 5: 380-1.
41. van Vliet EA, van Schaik R, Edelbroek PM, et al. Inhibition of the multidrug transporter P-glycoprotein improves seizure control in phenytoin-treated chronic epileptic rats. Epilepsia 2006; 47: 672-80.
42. Szakacs G, Paterson JK, Ludwig JA, et al. Targeting multidrug resistance in cancer. Nat Rev Drug Discov 2006; 5: 219-34.
43. Iannetti P, Parisi P, Spalice A, et al. Addition of verapamil in the treatment of severe myoclonic epilepsy in infancy. Epilepsy Res 2009; 85: 89-95.
44. Iannetti P, Spalice A, Parisi P. Calcium-channel blocker verapamil adminis- trationin prolonged and refractory status epilepticus. Epilepsia 2005; 46: 967-9