Saturable active efflux by P-glycoprotein and breast cancer resistance protein at the blood-brain barrier leads to nonlinear distribution of elacridar to the central nervous system

Journal of Pharmacology and Experimental Therapeutics

Volumn 345, Issue 1, 2013, Pages 111-124

  Sane, Ramola ^a   Agarwal, Sagar ^a   Mittapalli, Rajendar K ^a   Elmquist, William F ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BREAST CANCER RESISTANCE PROTEIN; DASATINIB; ELACRIDAR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; BCRP1 GENE; BLOOD BRAIN BARRIER; BRAIN CANCER; BRAIN LEVEL; CANCER RESISTANCE; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DOSE RESPONSE; DRUG CLEARANCE; DRUG DETERMINATION; DRUG DISTRIBUTION; DRUG DOSE INCREASE; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG PENETRATION; DRUG POTENTIATION; FEMALE; FRIEND LEUKEMIA VIRUS; GENE OVEREXPRESSION; GENOTYPE; LOW DRUG DOSE; MALE; MAXIMUM PLASMA CONCENTRATION; MDR1A GENE; MDR1B GENE; MOUSE; NONHUMAN; NONLINEAR SYSTEM; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN TRANSPORT; SINGLE DRUG DOSE; TISSUE DISTRIBUTION; TUMOR CELL; VIRUS GENE; VIRUS STRAIN;

ACRIDINES; ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; BLOOD-BRAIN BARRIER; CELL CULTURE TECHNIQUES; CENTRAL NERVOUS SYSTEM; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; INJECTIONS, INTRAVENOUS; MADIN DARBY CANINE KIDNEY CELLS; MICE; MICE, KNOCKOUT; MODELS, BIOLOGICAL; NONLINEAR DYNAMICS; P-GLYCOPROTEIN; P-GLYCOPROTEINS; TETRAHYDROISOQUINOLINES; TISSUE DISTRIBUTION;

EID: 84875465379     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.112.199786     Document Type: Article

References (35)

1. Agarwal S and Elmquist WF (2012) Insight into the cooperation of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) at the blood-brain barrier: a case study examining sorafenib efflux clearance. Mol Pharm 9:678-684.
2. Agarwal S, Mittapalli RK, Zellmer DM, Gallardo JL, Donelson R, Seiler C, Decker SA, Santacruz KS, Pokorny JL, and Sarkaria JN, et al. (2012a) Active efflux of Dasatinib from the brain limits efficacy against murine glioblastoma: broad implications for the clinical use of molecularly targeted agents. Mol Cancer Ther 11:2183-2192.
3. Agarwal S, Sane R, Gallardo JL, Ohlfest JR, and Elmquist WF (2010) Distribution of gefitinib to the brain is limited by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2)-mediated active efflux. J Pharmacol Exp Ther 334: 147-155.
4. Agarwal S, Sane R, Oberoi R, Ohlfest JR, and Elmquist WF (2011a) Delivery of molecularly targeted therapy to malignant glioma, a disease of the whole brain. Expert Rev Mol Med 13:e17.
5. Agarwal S, Sane R, Ohlfest JR, and Elmquist WF (2011b) The role of the breast cancer resistance protein (ABCG2) in the distribution of sorafenib to the brain. J Pharmacol Exp Ther 336:223-233.
6. Agarwal S, Uchida Y, Mittapalli RK, Sane R, Terasaki T, and Elmquist WF (2012b) Quantitative proteomics of transporter expression in brain capillary endothelial cells isolated from P-glycoprotein (P-gp), breast cancer resistance protein (Bcrp), and P-gp/Bcrp knockout mice. Drug Metab Dispos 40:1164-1169.
7. Allen JD, Brinkhuis RF, Wijnholds J, and Schinkel AH (1999) The mouse Bcrp1/Mxr/ Abcp gene: amplification and overexpression in cell lines selected for resistance to topotecan, mitoxantrone, or doxorubicin. Cancer Res 59:4237-4241.
8. Bailer AJ (1988) Testing for the equality of area under the curves when using destructive measurement techniques. J Pharmacokinet Biopharm 16:303-309.
9. Bihorel S, Camenisch G, Lemaire M, and Scherrmann JM (2007) Influence of breast cancer resistance protein (Abcg2) and p-glycoprotein (Abcb1a) on the transport of imatinib mesylate (Gleevec) across the mouse blood-brain barrier. J Neurochem 102:1749-1757.
10. Breedveld P, Pluim D, Cipriani G, Wielinga P, van Tellingen O, Schinkel AH, and Schellens JH (2005) The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients. Cancer Res 65:2577-2582.
11. Chen Y, Agarwal S, Shaik NM, Chen C, Yang Z, and Elmquist WF (2009) Pglycoprotein and breast cancer resistance protein influence brain distribution of dasatinib. J Pharmacol Exp Ther 330:956-963.
12. Dai H, Marbach P, Lemaire M, Hayes M, and Elmquist WF (2003) Distribution of STI-571 to the brain is limited by P-glycoprotein-mediated efflux. J Pharmacol Exp Ther 304:1085-1092.
13. de Vries NA, Zhao J, Kroon E, Buckle T, Beijnen JH, and van Tellingen O (2007) P-glycoprotein and breast cancer resistance protein: two dominant transporters working together in limiting the brain penetration of topotecan. Clin Cancer Res 13:6440-6449.
14. Dörner B, Kuntner C, Bankstahl JP, Bankstahl M, Stanek J, Wanek T, Stundner G, Mairinger S, Löscher W, and Müller M, et al. (2009) Synthesis and small-animal positron emission tomography evaluation of [11C]-elacridar as a radiotracer to assess the distribution of P-glycoprotein at the blood-brain barrier. J Med Chem 52: 6073-6082.
15. Hartz AM and Bauer B (2010) Regulation of ABC transporters at the blood-brain barrier: new targets for CNS therapy. Mol Interv 10:293-304.
16. Hubensack M, Müller C, Höcherl P, Fellner S, Spruss T, Bernhardt G, and Buschauer A (2008) Effect of the ABCB1 modulators elacridar and tariquidar on the distribution of paclitaxel in nude mice. J Cancer Res Clin Oncol 134:597-607.
17. Hyafil F, Vergely C, Du Vignaud P, and Grand-Perret T (1993) In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative. Cancer Res 53:4595-4602.
18. Kawamura K, Yamasaki T, Konno F, Yui J, Hatori A, Yanamoto K, Wakizaka H, Ogawa M, Yoshida Y, and Nengaki N, et al. (2011a) Synthesis and in vivo evaluation of 18F-fluoroethyl GF120918 and XR9576 as positron emission tomography probes for assessing the function of drug efflux transporters. Bioorg Med Chem 19:861-870.
19. Kawamura K, Yamasaki T, Konno F, Yui J, Hatori A, Yanamoto K, Wakizaka H, Takei M, Kimura Y, and Fukumura T, et al. (2011b) Evaluation of limiting brain penetration related to P-glycoprotein and breast cancer resistance protein using [11C]GF120918 by PET in mice. Mol Imaging Biol 13:152-160.
20. Kemper EM, van Zandbergen AE, Cleypool C, Mos HA, Boogerd W, Beijnen JH, and van Tellingen O (2003) Increased penetration of paclitaxel into the brain by inhibition of P-glycoprotein. Clin Cancer Res 9:2849-2855.
21. Kodaira H, Kusuhara H, Ushiki J, Fuse E, and Sugiyama Y (2010) Kinetic analysis of the cooperation of P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp/Abcg2) in limiting the brain and testis penetration of erlotinib, flavopiridol, and mitoxantrone. J Pharmacol Exp Ther 333:788-796.
22. Lagas JS, van Waterschoot RA, Sparidans RW, Wagenaar E, Beijnen JH, and Schinkel AH (2010) Breast cancer resistance protein and P-glycoprotein limit sorafenib brain accumulation. Mol Cancer Ther 9:319-326.
23. Lagas JS, van Waterschoot RA, van Tilburg VA, Hillebrand MJ, Lankheet N, Rosing H, Beijnen JH, and Schinkel AH (2009) Brain accumulation of dasatinib is restricted by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and can be enhanced by elacridar treatment. Clin Cancer Res 15:2344-2351.
24. Lu C and Shervington A (2008) Chemoresistance in gliomas. Mol Cell Biochem 312: 71-80.
25. Mittapalli RK, Vaidhyanathan S, Dudek AZ, and Elmquist WF (2012a) Mechanisms limiting distribution of the BRAFV600E inhibitor dabrafenib to the brain: implications for the treatment of melanoma brain metastases. J Pharmacol Exp Ther DOI: 10.1124/jpet.112.201475 [published ahead of print].
26. Mittapalli RK, Vaidhyanathan S, Sane R, and Elmquist WF (2012b) Impact of Pglycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on the brain distribution of a novel BRAF inhibitor: vemurafenib (PLX4032). J Pharmacol Exp Ther 342:33-40.
27. Nedelman JR, Gibiansky E, and Lau DT (1995) Applying Bailer's method for AUC confidence intervals to sparse sampling. Pharm Res 12:124-128.
28. 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.
29. 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.
30. Reardon DA, Vredenburgh JJ, Desjardins A, Peters KB, Sathornsumetee S, Threatt S, Sampson JH, Herndon JE, 2nd, Coan A, and McSherry F, et al. (2012) Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant glioma. J Neurooncol 108:499-506.
31. Sane R, Agarwal S, and Elmquist WF (2012) Brain distribution and bioavailability of elacridar after different routes of administration in the mouse. Drug Metab Dispos 40:1612-1619.
32. Tang SC, Lagas JS, Lankheet NA, Poller B, Hillebrand MJ, Rosing H, Beijnen JH, and Schinkel AH (2012) Brain accumulation of sunitinib is restricted by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and can be enhanced by oral elacridar and sunitinib coadministration. Int J Cancer 130: 223-233.
33. Wang T, Agarwal S, and Elmquist WF (2012) Brain distribution of cediranib is limited by active efflux at the blood-brain barrier. J Pharmacol Exp Ther 341: 386-395.
34. Ward KW and Azzarano LM (2004) Preclinical pharmacokinetic properties of the P-glycoprotein inhibitor GF120918A (HCl salt of GF120918, 9,10-dihydro-5- methoxy-9-oxo-N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl] phenyl]-4-acridine-carboxamide) in the mouse, rat, dog, and monkey. J Pharmacol Exp Ther 310:703-709.
35. Warren KE, Patel MC, McCully CM, Montuenga LM, and Balis FM (2000) Effect of P-glycoprotein modulation with cyclosporin A on cerebrospinal fluid penetration of doxorubicin in non-human primates. Cancer Chemother Pharmacol 45:207-212.