Validation and application of Caco-2 assays for the in vitro evaluation of development candidate drugs as substrates or inhibitors of P-glycoprotein to support regulatory submissions

Xenobiotica

Volumn 38, Issue 7-8, 2008, Pages 1140-1164

  Elsby, R ^a   Surry, D D ^a   Smith, V N ^a   Gray, A J ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

Caco 2; In vitro; P glycoprotein; Regulatory; Transporters; US Food and Drug Administration (USFDA); Validation

Indexed keywords

DIGOXIN; DIPYRIDAMOLE; GLYCOPROTEIN P INHIBITOR; KETOCONAZOLE; LORATADINE; MANNITOL; PROBENECID; PROPRANOLOL; QUINIDINE; VERAPAMIL;

ARTICLE; CLINICAL EVALUATION; IC 50; IN VITRO STUDY; PROTEIN EXPRESSION; PROTEIN TRANSPORT;

ANTIFUNGAL AGENTS; BIOLOGICAL ASSAY; CACO-2 CELLS; DRUG APPROVAL; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HUMANS; KETOCONAZOLE; P-GLYCOPROTEIN; QUINIDINE; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 48749121103     PISSN: 00498254     EISSN: 13665928     Source Type: Journal    
DOI: 10.1080/00498250802050880     Document Type: Article

References (39)

1. Alderman CP, Allcroft PD. 1998. Digoxin-itraconazole interaction: Possible mechanism. Annals of Pharmacotherapy 31:438-440.
2. Artursson P, Karlsson J. 1991. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelia (Caco-2) cells. Biochemical and Biophysical Research Communications 175:880-890.
3. Ayrton A, Morgan P. 2001. Role of transport proteins in drug absorption, distribution and excretion. Xenobiotica 31:469-497.
4. Balimane PV, Han Y-H, Chong S. 2006. Current industrial practices of assessing permeability and P-glycoprotein interaction. AAPS Journal 8:1-13.
5. Bjornsson TD, Callaghan JT, Einolf HJ, Fischer V, Gan L, Grimm S, Kao J, King SP, Miwa G, Ni L, et al. 2003. The conduct of in vitro and in vivo drug-drug interaction studies: A pharmaceutical research and manufacturers of America (PhRMA) perspective. Drug Metabolism and Disposition 31:815-832.
6. Englund G, Rorsman F, Rönnblom A, Karlbom U, Lazorova L, Gråsjö J, Kindmark A, Artursson P. 2006. Regional levels of drug transporters along the human intestinal tract: Co-expression of ABC and SLC transporters and comparison with Caco-2 cells. European Journal of Pharmaceutical Sciences 29:269-277.
7. Fromm MF, Kim RB, Stein CM, Wilkinson GR, Roden DM. 1999. Inhibition of p-glycoprotein-mediated drug transport: A unifying mechanism to explain the interaction between digoxin and quinidine. Circulation 99:472-474.
8. Greiner B, Eichelbaum M, Fritz P, Kreichgauer HP, Von RO, Zundler J, Kroemer HK. 1999. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. Journal of Clinical Investigation 104:147-153.
9. Gupta A, Unadkat JD, Mao Q. 2007. Interactions of azole antifungal agents with the human breast cancer resistance protein (BCRP). Journal of Pharmaceutical Sciences 96:3226-3235.
10. Gutmann H, Fricker G, Török M, Michael S, Beglinger C, Drewe J. 1999. Evidence for different ABC-transporters in Caco-2 cells modulating drug uptake. Pharmaceutical Research 16:402-407.
11. Hedman A, Angelin B, Arvidsson A, Dahlqvist R, Nilsson B. 1990. Interactions in the renal and biliary elimination of digoxin: Stereoselective difference between quinine and quinidine. Clinical Pharmacology and Therapeutics 47:20-26.
12. Hilgendorf C, Ahlin G, Seithel A, Artursson P, Ungell A-L, Karlsson J. 2007. Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines. Drug Metabolism and Disposition 35:1333-1340.
13. Jalava KM, Partanen J, Neuvonen PJ. 1997. Itraconazole decreases renal clearance of digoxin. Therapeutic Drug Monitoring 19:609-613.
14. Keogh JP, Kunta JR. 2006. Development, validation and utility of an in vitro technique for assessment of potential clinical drug-drug interactions involving P-glycoprotein. European Journal of Pharmaceutical Sciences 27:543-554.
15. Kim RB. 2006. Transporters and drug discovery: Why, when, and how. Molecular Pharmaceutics 3:26-32.
16. Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, et al. 1999. Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharmaceutical Research 16:408-414.
17. Koren G, Woodland C, Ito S. 1998. Toxic digoxin-drug interactions: The major role of renal P-glycoprotein. Veterinary and Human Toxicology 40:45-46.
18. Kusuhara H, Sugiyama Y. 2002. Role of transporters in the tissue-selective distribution and elimination of drugs: Transporters in the liver, small intestine, brain and kidney. Journal of Controlled Release 78:43-54.
19. Martin C, Berridge G, Higgins CF, Mistry P, Charlton P, Callaghan R. 2000. Communication between multiple drug binding sites on P-glycoprotein. Molecular Pharmacology 58:624-632.
20. Mizuno N, Niwa T, Yotsumoto Y, Sugiyama Y. 2003. Impact of drug transporter studies on drug discovery and development. Pharmacological Reviews 55:425-461.
21. Müller J, Lips KS, Metzner L, Neubert RHH, Koepsell H, Brandsch M. 2005. Drug specificity and intestinal membrane localization of human organic transporters (OCT). Biochemical Pharmacology 70:1851-1860.
22. Partanen J, Jalava KM, Neuvonen PJ. 1996. Itraconazole increases serum digoxin concentration. Pharmacology and Toxicology 79:274-276.
23. Pederson KE, Christiansen BD, Klitgaard NA, Nielsen-Kudsk F. 1983. Effect of quinidine on digoxin bioavailability. European Journal of Clinical Pharmacology 24:41-47.
24. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS. 2001. Rational use of in vitro P-glycoprotein assays in drug discovery. Journal of Pharmacology and Experimental Therapeutics 299:620-628.
25. Prime-Chapman HM, Fearn RA, Cooper AE, Moore V, Hirst BH. 2004. Differential multidrug resistance-associated protein 1 through 6 isoform expression and function in human intestinal epithelial Caco-2 cells. Journal of Pharmacology and Experimental Therapeutics 311:476-484.
26. Rosenberg MF, Velarde G, Ford RC, Martin C, Berridge G, Kerr ID, Callaghan R, Schmidin A, Wooding C, Linton KJ, et al. 2001. Repacking of the transmembrane domains of P-glycoprotein during the transport ATPase cycle. EMBO Journal 20:5615-5625.
27. Sadaque AJM, Wandel C, He H, Shah S, Wood AJJ. 2000. Increased drug delivery to the brain by P-glycoprotein inhibition. Clinical Pharmacology and Therapeutics 68:231-237.
28. Schinkel AH. 1999. P-glycoprotein, a gatekeeper in the blood-brain barrier. Advanced Drug Delivery Reviews 36:179-194.
29. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J. 2003. Comparison of in vitro P-glycoprotein screening assays: Recommendations for their use in drug discovery. Journal of Medicinal Chemistry 46:1716-1725.
30. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC. 1987. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues 84:7735-7738.
31. Troutman MD, Thakker DR. 2003. Efflux ratio cannot assess P-glycoprotein mediated attenuation of absorptive transport: Asymmetric effect of P-glycoprotein on absorptive and secretory transport across Caco-2 cell monolayers. Pharmaceutical Research 20:1200-1209.
32. US Food and Drug Administration. 2006. Draft guidance for industry: Drug interaction studies - study design, data analysis, and implications for dosing and labeling (available at: http://www.fda.gov/cder/guidance.com).
33. Walgren RA, Walle T. 1999. The influence of plasma binding on absorption/exsorption in the Caco-2 model of human intestinal absorption. Journal of Pharmacy and Pharmacology 51:1037-1040.
34. Wang RB, Kuo CL, Lien LL, Lien EJ. 2003. Structure-activity relationships: Analyses of P-glycoprotein substrates and inhibitors. Journal of Clinical Pharmacy and Therapeutics 28:203-228.
35. Xia CQ, Liu N, Yang D, Miwa G, Gan L-S. 2005. Expression, localization, and functional characteristics of breast cancer resistance protein in Caco-2 cells. Drug Metabolism and Disposition 33:637-643.
36. Xia CQ, Milton MN, Gan L-S. 2007. Evaluation of drug-transporter interactions using in vitro and in vivo models. Current Drug Metabolism 8:341-363.
37. Yengi LG, Leung L, Kao J. 2007. The evolving role of drug metabolism in drug discovery and development. Pharmaceutical Research 24:842-858.
38. Zelcer N, Huisman MT, Reid G, Wielinga P, Breedveld P, Kuil A, Knipscheer P, Schellens JHM, Schinkel AH, Borst P. 2003. Evidence of two interacting ligand binding sites in human multidrug resistance protein 2 (ATP binding cassette C2). Journal of Biological Chemistry 278:23538-23544.
39. Zhang L, Strong JM, Qiu W, Lesko LJ, Huang S-M. 2006. Scientific perspectives on drug transporters and their role in drug interactions. Molecular Pharmaceutics 3:62-69.