Pharmacokinetics, distribution, metabolism, and excretion of deferasirox and its iron complex in rats

Drug Metabolism and Disposition

Volumn 36, Issue 12, 2008, Pages 2523-2538

  Bruin, Gerard J M ^a   Faller, Thomas ^a   Wiegand, Hansjörg ^a   Schweitzer, Alain ^a   Nick, Hanspeter ^a   Schneider, Josef ^a,b   Boernsen, K Olaf ^a   Waldmeier, Felix ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON 14; DEFERASIROX; DRUG METABOLITE; IRON COMPLEX; MULTIDRUG RESISTANCE PROTEIN 2;

ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; AUTORADIOGRAPHY; BETA THALASSEMIA; BILIARY EXCRETION; BREAST MILK; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DISPOSITION; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG EXCRETION; DRUG FECES LEVEL; DRUG GLUCURONIDATION; DRUG HALF LIFE; DRUG HYDROXYLATION; DRUG INDICATION; DRUG METABOLISM; DRUG STRUCTURE; ENTEROHEPATIC CIRCULATION; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IRON OVERLOAD; ISOTOPE LABELING; LIQUID SCINTILLATION COUNTING; LIVER CLEARANCE; MALE; MASS SPECTROMETRY; MAXIMUM PLASMA CONCENTRATION; MEAN RESIDENCE TIME; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PLACENTAL TRANSFER; PRIORITY JOURNAL; RAT; SICKLE CELL ANEMIA; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION;

ANIMALS; ANIMALS, SUCKLING; ATP-BINDING CASSETTE TRANSPORTERS; BENZOIC ACIDS; BILE; BLOOD CHEMICAL ANALYSIS; ENTEROHEPATIC CIRCULATION; FECES; FEMALE; FETUS; IRON; IRON CHELATING AGENTS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MASS SPECTROMETRY; MILK, HUMAN; MODELS, BIOLOGICAL; MOLECULAR STRUCTURE; PLACENTA; PREGNANCY; RATS; RATS, LONG-EVANS; RATS, TRANSGENIC; RATS, WISTAR; TISSUE DISTRIBUTION; TRIAZOLES; URINE;

ANIMALIA; RATTUS;

EID: 57349185625     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.108.022962     Document Type: Article

References (35)

1. Bax A and Summers MF (1986) Proton and carbon-13 assignments from sensitivity-enhanced detection of heteronuclear multiple-bond connectivity by 2D multiple quantum NMR. J Am Chem Soc 108:2093-2094.
2. Begtrup M, Elguero J, and Faure R (1988) Effect of N-substituents on the carbon-13 NMR parameters of azoles. Magn Reson Chem 26:134-151.
3. Borst P, Zelcer N, and van de Wetering K (2006) MRP2 and 3 in health and disease. Cancer Lett 234:51-61.
4. Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, Allen CJ, Farrell DE, and Harris JW (1994) Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 331:567-573.
5. Chan LM, Lowes S, and Hirst BH (2004) The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability. Eur J Pharm Sci 21:25-51.
6. Cohen AR and Martin MB (2001) Iron chelation therapy in sickle cell disease. Semin Hematol 38 (1 Suppl 1):69-72.
7. Davies B and Morris T (1993) Physiological parameters in laboratory animals and humans. Pharm Res 10:1093-1095.
8. Dietrich CG, de Waart DR, and Ottenhoff R (2001) Mrp2-deficiency in the rat impairs biliary and intestinal excretion and influences metabolism and disposition of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP). Carcionogenesis 22:805-811.
9. Gabutti V and Piga A (1996) Results of long-term iron-chelating therapy. Acta Haematol 95:26-36.
10. Hamaoka T (1990) Autoradiography of a new era replacing traditional X-ray film. Cell Technol 456-462.
11. Harkness JE (2001) What's your diagnosis? Hair loss in lactating rats. Lab Anim (NY) 30:21-22.
12. Hershko C, Konijn AM, Nick HP, Breuer W, Cabantchik ZI, and Link G (2001) ICL670A: a new synthetic oral chelator: evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture. Blood 97:1115-1122.
13. Huang XP, Spino M, and Thiessen JJ (2006) Transport kinetics of iron chelators and their chelates in Caco-2 cells. Pharm Res 23:280-290.
14. Johnston RF, Pickett SC, and Barker DL (1990) Autoradiography using storage phosphor technology. Electrophoresis 11:355-360.
15. Kay LE, Keifer P, and Saarinen T (1992) Pure absorption gradient enhanced heteronuclear single quantum correlation spectroscopy with improved sensitivity. J Am Chem Soc 114:10663-10665.
16. - rats. Xenobiotica 33:1027-1042.
17. König J, Rost D, Cui Y, and Keppler D (1999) Characterization of the human multidrug resistance protein isoform Mrp3 localized to the basolateral hepatocyte membrane. Hepatology 29:1156-1163.
18. Miyahara J (1989) Visualizing things never seen before - the imaging plate: a new radiation image sensor. Chem Today 29-36.
19. Nick H, Acklin P, Lattmann R, Buehlmayer P, Hauffe S, Schupp J, and Alberti D (2003) Development of tridentate iron chelators: from desferrithiocin to ICL670. Curr Med Chem 10:1065-1076.
20. Nick HP, Acklin P, and Faller B (2000) A new, potent, orally active iron chelator, in Iron Chelators: New Development Strategies (Badman DG, Bergeron RJ, and Brittenham GM eds) pp 311-333, The Saratoga Group, Ponte Verde Beach, FL.
21. Olivieri NF (1999) The β-thalassemias. N Engl J Med 341:99-109.
22. Olivieri NF and Brittenham GM (1997) Iron-chelating therapy and the treatment of thalassemia. Blood 89:739-761.
23. Palmer AG III, Cavanagh J, Wright PE, and Rance M (1991) Sensitivity improvement in proton-detected two-dimensional heteronuclear correlation NMR spectroscopy. J Magn Reson 93:151-170.
24. Rath L and Hutchison M (1989) A new method of bile duct cannulation allowing bile collection and re-infusion in the conscious rat. Lab Anim 23:163-168.
25. Rouan MC, Marfil F, Mangoni P, Séchaud R, Humbert H, and Maurer G (2001) Determination of a new oral iron chelator, ICL670, and its iron complex in plasma by high-performance liquid chromatography and ultraviolet detection. J Chromatogr B Biomed Sci Appl 755:203-213.
26. Schleucher J, Schwendinger M, Sattler M, Schmidt P, Schedletzky O, Glaser SJ, Sørensen OW, and Griesinger C (1994) A general enhancement scheme in heteronuclear multidimensional NMR employing pulsed field gradients. J Biomol NMR 4:301-306.
27. Schweitzer A, Fahr A, and Niederberger W (1987) A simple method for the quantitation of 14C-whole-body autoradiograms. Int J Rad Appl Instrum [A] 38:329-333.
28. Shigematsu A (1992) Bao-Bei, or the powerful technology, in science of whole-body metabolism. Radioluminography 3:1-15.
29. Shionoya S (1992) Mechanistic approach toward photostimulated luminography. Radioluminograpy 1-15.
30. Shipkova M, Armstrong VW, Oellerich M, and Wieland E (2003) Acyl glucuronide drug metabolites: toxicological and analytical implications. Ther Drug Monit 25:1-16.
31. Steinhauser S, Heinz U, Bartholoma M, Weyhermuller T, Nick H, and Hegetschweiler K (2004) Complex formation of ICL670 and related ligands with Fe III and Fe II. Eur J Inorg Chem 21:4177-4192.
32. Ullberg S (1977) The technique of whole-body autoradiography: cryosectioning of large specimens, in Science Tools (Alvfeldt O ed) pp 2-29, LDK-produkter AB, Sweden.
33. von Kienlin M, Moonene CTW, von der Toorn A, and van Zijl PCM (1991) Rapid recording of solvent-suppressed 2D COSY spectra with inherent quadrature detection using pulsed field gradients. J Magn Reson 93:423-429.
34. Weiss HM, Fresneau M, Camenisch GP, Kretz O, and Gross G (2006) In vitro blood distribution and plasma protein binding of the iron chelator deferasirox (ICL670) and its iron complex Fe-[ICL670]2, for rat, marmoset, rabbit, mouse, dog and human. Drug Metab Dispos 34:971-975.
35. Willker W, Leibfritz D, Kerssebaum R, and Bermel W (1993) Gradient selection in inverse heteronuclear correlation spectroscopy. Magn Reson Chem 31:287-292.