In vitro characterization of axitinib interactions with human efflux and hepatic uptake transporters: Implications for disposition and drug interactions

Drug Metabolism and Disposition

Volumn 41, Issue 8, 2013, Pages 1575-1583

  Reyner, Eric L ^a   Sevidal, Samantha ^a   West, Mark A ^a   Clouser Roche, Andrea ^a   Freiwald, Sascha ^a   Fenner, Katherine ^b   Ullah, Mohammed ^b   Lee, Caroline A ^a   Smith, Bill J ^a  

^a PFIZER INC   (United States)

^b Sandwich Laboratories   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; AXITINIB; BREAST CANCER RESISTANCE PROTEIN; CARBON 14; DIGOXIN; MULTIDRUG RESISTANCE PROTEIN; MULTIDRUG RESISTANCE PROTEIN 1; ORGANIC ANION TRANSPORTER 2; ORGANIC ANION TRANSPORTING POLYPEPTIDE 1B3; ORGANIC CATION TRANSPORTER; RIFAMPICIN; TOPOTECAN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG ABSORPTION; DRUG DISPOSITION; DRUG DISTRIBUTION; DRUG INTERACTION; DRUG PENETRATION; DRUG SOLUBILITY; DRUG TISSUE LEVEL; DRUG TRANSPORT; EMBRYO; GASTROINTESTINAL TRACT; HUMAN; HUMAN CELL; IN VITRO STUDY; LIVER CELL; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; TISSUE DISTRIBUTION; WHOLE BODY AUTORADIOGRAPHY;

ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; AUTORADIOGRAPHY; CACO-2 CELLS; DRUG INTERACTIONS; HEPATOCYTES; HUMANS; IMIDAZOLES; INDAZOLES; LIVER; MICE; NEOPLASM PROTEINS; P-GLYCOPROTEIN; PERMEABILITY; PROTEIN KINASE INHIBITORS; RISK ASSESSMENT; SOLUBILITY;

EID: 84880654833     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.113.051193     Document Type: Article

References (47)

1. Bender SL, Kania, RS, and McTigue, MA (2004) inventors, Pfizer Inc., assignee. Crystal structure of human VEGFR2 kinase domain-ligand complexes and use of the atomic coordinates in drug discovery. International patent WO 2004/092217:A1. 2005 Apr 4.
2. Bi YA, Kimoto E, Sevidal S, Jones HM, Barton HA, Kempshall S, Whalen KM, Zhang H, Ji C, and Fenner KS, et al. (2012) In vitro evaluation of hepatic transporter-mediated clinical drugdrug interactions: hepatocyte model optimization and retrospective investigation. Drug Metab Dispos 40:1085-1092.
3. Brennan M, Williams JA, Chen Y, Tortorici M, Pithavala Y, and Liu YC (2012) Meta-Analysis of contribution of genetic polymorphisms in drug-metabolizing enzymes or transporters to axitinib pharmacokinetics. Eur J Clin Pharmacol 68:645-655.
4. Carcaboso AM, Elmeliegy MA, Shen J, Juel SJ, Zhang ZM, Calabrese C, Tracey L, Waters CM, and Stewart CF (2010) Tyrosine kinase inhibitor gefitinib enhances topotecan penetration of gliomas. Cancer Res 70:4499-4508.
5. Center for Drug Evaluation and Research (CDER) (2012a) Application Number: 202324Orig1s000, Clinical Pharmacology and Biopharmaceutics Review. http://www.accessdata.fda.gov/drugsatfda-docs/nda/2012/ 202324Orig1s000ClinPharmR.pdf
6. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER).
7. Center for Drug Evaluation and Research (CDER) (2012b) Drug Interaction Studies -Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations Draft Guidance. http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/ucm292362.pdf
8. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER).
9. Chen Y, Agarwal S, Shaik NM, Chen C, Yang Z, and Elmquist WF (2009) P-glycoprotein and breast cancer resistance protein influence brain distribution of dasatinib. J Pharmacol Exp Ther 330:956-963.
10. Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, and Bycott P, et al. (2008) Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol 26:4708-4713.
11. Committee for Human Medicinal Products (CHMP) (2012c) Guideline on the Investigation of Drug Interactions. http://www.ema.europa.eu/docs/en-GB/ document-library/Scientific-guideline/2012/07/WC500129606.pdf, European Medicines Agency, Committee for Human Medicinal Products (CHMP).
12. Cook JA, Feng B, Fenner KS, Kempshall S, Liu R, Rotter C, Smith DA, Troutman MD, Ullah M, and Lee CA (2010) Refining the in vitro and in vivo critical parameters for P-glycoprotein, [I]/IC50 and [I2]/IC50, that allow for the exclusion of drug candidates from clinical digoxin interaction studies. Mol Pharm 7:398-411.
13. Di L, Whitney-Pickett C, Umland JP, Zhang H, Zhang X, Gebhard DF, Lai Y, Federico JJ, 3rd, Davidson RE, and Smith R, et al. (2011) Development of a new permeability assay using lowefflux MDCKII cells. J Pharm Sci 100:4974-4985.
14. Dohse M, Scharenberg C, Shukla S, Robey RW, Volkmann T, Deeken JF, Brendel C, Ambudkar SV, Neubauer A, and Bates SE (2010) Comparison of ATP-binding cassette transporter interactions with the tyrosine kinase inhibitors imatinib, nilotinib, and dasatinib. Drug Metab Dispos 38:1371-1380.
15. Evers R, Kool M, Smith AJ, van Deemter L, de Haas M, and Borst P (2000) Inhibitory effect of the reversal agents V-104, GF120918 and Pluronic L61 on MDR1 Pgp-, MRP1-and MRP2-mediated transport. Br J Cancer 83:366-374.
16. Fenner KS, Troutman MD, Kempshall S, Cook JA, Ware JA, Smith DA, and Lee CA (2009) Drug-drug interactions mediated through P-glycoprotein: clinical relevance and in vitro-in vivo correlation using digoxin as a probe drug. Clin Pharmacol Ther 85:173-181.
17. Folkman J, Merler E, Abernathy C, and Williams G (1971) Isolation of a tumor factor responsible for angiogenesis. J Exp Med 133:275-288.
18. Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, Chu X, Dahlin A, Evers R, Fischer V, and Hillgren KM, et al.; International Transporter Consortium (2010) Membrane transporters in drug development. Nat Rev Drug Discov 9:215-236.
19. Goldstein R, Pickering L, and Larkin J (2010) Does axitinib (AG-01376) have a future role in metastatic renal cell carcinoma and other malignancies? Expert Rev Anticancer Ther 10: 1545-1557.
20. Hanahan D and Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353-364.
21. Hartmann JT, Haap M, Kopp HG, and Lipp HP (2009) Tyrosine kinase inhibitors -a review on pharmacology, metabolism and side effects. Curr Drug Metab 10:470-481.
22. Ho RH, Tirona RG, Leake BF, Glaeser H, Lee W, Lemke CJ, Wang Y, and Kim RB (2006) Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology 130:1793-1806.
23. Hu-Lowe DD, Zou HY, Grazzini ML, Hallin ME, Wickman GR, Amundson K, Chen JH, Rewolinski DA, Yamazaki S, and Wu EY, et al. (2008) Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res 14:7272-7283.
24. Inlyta. (2012) Prescribing information: Inlyta (axitinib) tablets for oral administration. Pfizer Labs, New York.
25. König J, Cui Y, Nies AT, and Keppler D (2000a) Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide. J Biol Chem 275:23161-23168.
26. König J, Cui Y, Nies AT, and Keppler D (2000b) A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane. Am J Physiol Gastrointest Liver Physiol 278:G156-G164.
27. Mita S, Suzuki H, Akita H, Hayashi H, Onuki R, Hofmann AF, and Sugiyama Y (2006) Inhibition of bile acid transport across Na+/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs. Drug Metab Dispos 34:1575-1581.
28. Nishizato Y, Ieiri I, Suzuki H, Kimura M, Kawabata K, Hirota T, Takane H, Irie S, Kusuhara H, and Urasaki Y, et al. (2003) Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics. Clin Pharmacol Ther 73:554-565.
29. Nozawa T, Minami H, Sugiura S, Tsuji A, and Tamai I (2005) Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms. Drug Metab Dispos 33:434-439.
30. Oostendorp RL, Buckle T, Beijnen JH, van Tellingen O, and Schellens JH (2009) The effect of P-gp (Mdr1a/1b), BCRP (Bcrp1) and P-gp/BCRP inhibitors on the in vivo absorption, distribution, metabolism and excretion of imatinib. Invest New Drugs 27:31-40.
31. Pithavala YK, Tong W, Mount J, Rahavendran SV, Garrett M, Hee B, Selaru P, Sarapa N, and Klamerus KJ (2012) Effect of ketoconazole on the pharmacokinetics of axitinib in healthy volunteers. Invest New Drugs 30:273-281.
32. Poller B, Iusuf D, Sparidans RW, Wagenaar E, Beijnen JH, and Schinkel AH (2011) Differential impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on axitinib brain accumulation and oral plasma pharmacokinetics. Drug Metab Dispos 39:729-735.
33. Polli JW, Humphreys JE, Harmon KA, Castellino S, O'Mara MJ, Olson KL, John-Williams LS, Koch KM, and Serabjit-Singh CJ (2008) The role of efflux and uptake transporters in [N-3-chloro-4-[(3-fluorobenzyl)oxy]phenyl-6-[5-([2- (methylsulfonyl)ethyl]aminomethyl)-2-furyl]-4-quinazolinamine (GW572016, lapatinib) disposition and drug interactions. Drug Metab Dispos 36:695-701.
34. Polli JW, Olson KL, Chism JP, John-Williams LS, Yeager RL, Woodard SM, Otto V, Castellino S, and Demby VE (2009) An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the central nervous system penetration of the tyrosine kinase inhibitor lapatinib (N-3-chloro-4-[(3-fluorobenzyl)oxy]phenyl-6-[5-([2-(methylsulfonyl)ethyl] aminomethyl)-2-furyl]-4-quinazolinamine; GW572016). Drug Metab Dispos 37:439-442.
35. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, and Rusakov IG, et al. (2011) Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378: 1931-1939.
36. Rixe O, Bukowski RM, Michaelson MD, Wilding G, Hudes GR, Bolte O, Motzer RJ, Bycott P, Liau KF, and Freddo J, et al. (2007) Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol 8:975-984.
37. Romaine SP, Bailey KM, Hall AS, and Balmforth AJ (2010) The influence of SLCO1B1 (OATP1B1) gene polymorphisms on response to statin therapy. Pharmacogenomics J 10:1-11.
38. Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, Pithavala YK, Reich SD, Freddo JL, and Wilding G (2005) Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol 23: 5474-5483.
39. Schinkel AH, Wagenaar E, van Deemter L, Mol CA, and Borst P (1995) Absence of the mdr1a PGlycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest 96:1698-1705.
40. Shimizu M, Fuse K, Okudaira K, Nishigaki R, Maeda K, Kusuhara H, and Sugiyama Y (2005) Contribution of OATP (organic anion-transporting polypeptide) family transporters to the hepatic uptake of fexofenadine in humans. Drug Metab Dispos 33:1477-1481.
41. Shukla S, Robey RW, Bates SE, and Ambudkar SV (2009) Sunitinib (Sutent, SU11248), a smallmolecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2. Drug Metab Dispos 37:359-365.
42. Solowiej J, Bergqvist S, McTigue MA, Marrone T, Quenzer T, Cobbs M, Ryan K, Kania RS, Diehl W, and Murray BW (2009) Characterizing the effects of the juxtamembrane domain on vascular endothelial growth factor receptor-2 enzymatic activity, autophosphorylation, and inhibition by axitinib. Biochemistry 48:7019-7031.
43. Tang-Wai DF, Kajiji S, DiCapua F, de Graaf D, Roninson IB, and Gros P (1995) Human (MDR1) and mouse (mdr1, mdr3) P-glycoproteins can be distinguished by their respective drug resistance profiles and sensitivity to modulators. Biochemistry 34:32-39.
44. van Erp NP, Gelderblom H, and Guchelaar HJ (2009) Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev 35:692-706.
45. Xiao Y, Davidson R, Smith A, Pereira D, Zhao S, Soglia J, Gebhard D, de Morais S, and Duignan DB (2006) A 96-well efflux assay to identify ABCG2 substrates using a stably transfected MDCK II cell line. Mol Pharm 3:45-54.
46. Zhang L, Zhang YD, Strong JM, Reynolds KS, and Huang SM (2008) A regulatory viewpoint on transporter-based drug interactions. Xenobiotica 38:709-724.
47. Zientek M (2010) In vitro kinetic characterization of axitinib metabolism to estimate the clinical implications of genetic polymorphisms, in ISSX Online Abstracts of the Workshop on Genetic Polymorphisms in Drug Disposition; 2010 April 11-13; Indianapolis, IN, http://issx.confex. com/issx/gpddw/webprogram/ Paper19628.html, International Society for the Study of Xenobiotics, Washington, DC.