Interplay of transporters and enzymes in the Caco-2 cell monolayer: I. Effect of altered apical secretion

Biopharmaceutics and Drug Disposition

Volumn 31, Issue 4, 2010, Pages 215-227

  Fan, Jianghong ^a   Maeng, Han Joo ^a   Pang, K Sandy ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

Caco 2; Catenary model; Excretion; Linear and non linear conditions; Metabolism; See saw phenomenon; Transporter enzyme interplay

Indexed keywords

CARRIER PROTEIN; ENZYME; DRUG;

ACTIVE TRANSPORT; APICAL MEMBRANE; ARTICLE; BASOLATERAL MEMBRANE; CELL STRAIN CACO 2; DRUG ABSORPTION; DRUG CLEARANCE; DRUG ELIMINATION; DRUG METABOLISM; HUMAN; HUMAN CELL; MEAN RESIDENCE TIME; PASSIVE TRANSPORT; BIOLOGICAL MODEL; METABOLISM; TRANSPORT AT THE CELLULAR LEVEL;

BIOLOGICAL TRANSPORT; CACO-2 CELLS; ENZYMES; HUMANS; MODELS, BIOLOGICAL; PHARMACEUTICAL PREPARATIONS;

EID: 77955302704     PISSN: 01422782     EISSN: 1099081X     Source Type: Journal    
DOI: 10.1002/bdd.704     Document Type: Article

References (41)

1. Suzuki H, Sugiyama Y. Role of metabolic enzymes and efflux transporters in the absorption of drugs from the small intestine. Eur J Pharm Sci 2000; 12: 3-12.
2. Shitara Y, Horie T, Sugiyama Y. Transporters as a determinant of drug clearance and tissue distribution. Eur J Pharm Sci 2006; 27: 425-446.
3. Thelen K, Dressman JB. Cytochrome P450-mediated metabolism in the human gut wall. J Pharm Pharmacol 2009; 61: 541-558.
4. Thummel KE, Wilkinson GR. In vitro and in vivo drug interactions involving human CYP3A. Annu Rev Pharmacol Toxicol 1998; 38: 389-430.
5. Lown KS, Mayo RR, Leichtman AB, et al. Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclo-sporine. Clin Pharmacol Ther 1997; 62: 248-260.
6. Gramatté T, Oertel R. Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil. Clin Pharmacol Ther 1999; 66: 239-245.
7. Greiner B, Eichelbaum M, Fritz P, et al. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J Clin Invest 1999; 104: 147-153.
8. Urquhart BL, Tirona RG, Kim RB. Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interindividual variability in response to drugs. J Clin Pharmacol 2007; 47: 566-578.
9. Fan J, Liu S, Du Y, Morrison J, Shipman R, Pang KS. Up-regulation of transporters and enzymes by the vitamin D receptor ligands, 1a, 25-dihydroxyvitamin D3 and vitamin D analogs, in the Caco-2 cell monolayer. J Pharmacol Exp Ther 2009; 330: 389-402.
10. 3 triggered vitamin D receptor and farnesoid X receptor-like effects in rat intestine and liver in vivo. Biopharm Drug Dispos 2009; 30: 457-475.
11. Cummins CL, JacobsenW, ChristiansU, Benet LZ. CYP3A4-transfected Caco-2 cells as a tool for understanding biochemical absorption barriers: studies with sirolimus and midazolam. J Pharmacol Exp Ther 2004; 308: 143-155.
12. Srinivas NR. Dual drug interactions via P-glyco-protein (P-gp)/cytochrome P450 (CYP3A4) interplay: recent case study of oral atorvastatin and verapamil. Eur J Clin Pharmacol 2008; 64: 1135-1136.
13. Shibata N, Gao W, Okamoto H, et al. Drug interactions between HIV protease inhibitors based on physiologically-based pharmacokinetic model. J Pharm Sci 2002; 91: 680-689.
14. Zhang Y, Guo X, Lin ET, Benet LZ. Overlapping substrate specificities of cytochrome P450 3A and P-glycoprotein for a novel cysteine protease inhibitor. Drug Metab Dispos 1998; 26: 360-366.
15. Wacher VJ, Silverman JA, Zhang Y, Benet LZ. Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. JPharm Sci 1998; 87:1322-1330.
16. Schuetz EG, Schinkel AH. Drug disposition as determined by the interplay between drug-transporting and drug-metabolizing systems. J Biochem Mol Toxicol 1999; 13: 219-222.
17. Tachibana T, Kato M, Watanabe T, Mitsui T, Sugiyama Y. Method for predicting the risk of drug-drug interactions involving inhibition of intestinal CYP3A4 and P-glycoprotein. Xenobiotica 2009; 39: 430-443.
18. Fisher JM, Wrighton SA, Watkins PB, et al. First-pass midazolam metabolism catalyzed by 1α, 25-dihydroxyvitamin D3-modified Caco-2 cell monolayers. J Pharmacol Exp Ther 1999; 289: 1134-1142.
19. Hochman JH, Chiba M, Nishime J, Yamazaki M, Lin JH. Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P-450 3A4. J Pharmacol Exp Ther 2000; 292: 310-318.
20. Cummins CL, Jacobsen W, Benet LZ. Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002; 300: 1036-1045.
21. Hochman JH, Chiba M, Yamazaki M, Tang C, Lin JH. P-glycoprotein-mediated efflux of indinavir metabolites in Caco-2 cells expressing cytochrome P450 3A4. J Pharmacol Exp Ther 2001; 298: 323-330.
22. Benet LZ, Cummins CL, Wu CY. Unmasking the dynamic interplay between efflux transporters and metabolic enzymes. Int J Pharm 2004; 277: 3-9.
23. Christians U, Schmitz V, Haschke M. Functional interactions between P-glycoprotein and CYP3A in drug metabolism. Expert Opin Drug Metab Toxicol 2005; 1: 641-654.
24. Mouly SJ, Paine MF, Watkins PB. Contributions of CYP3A4, P-glycoprotein, and serum protein binding to the intestinal first-pass extraction of saquinavir. J Pharmacol Exp Ther 2004; 308: 941-948.
25. Benet LZ. The drug transporter-metabolism alliance: uncovering and defining the interplay. Mol Pharm 2009; 6: 1631-1643.
26. Sun H, Pang KS. Permeability, transport, and metabolism of solutes in Caco-2 cell monolayers: a theoretical study. Drug Metab Dispos 2008; 36: 102-123.
27. Tam D, Sun H, Pang KS. Influenceof P-glycoprotein, transfer clearances, and drug binding on intestinal metabolism in Caco-2 cell monolayers or membrane preparations: a theoretical analysis. Drug Metab Dispos 2003; 31: 1214-1226.
28. Sun H, Chow EC, Liu S, Du Y, Pang KS. The Caco-2 cell monolayer: usefulness and limitations. Expert Opin Drug Metab Toxicol 2008; 4: 395-411.
29. Pang KS, Maeng H-J, Fan J. Interplay of transporters and enzymes in drug and metabolite processing. Mol Pharm 2009; 6: 1734-1755.
30. Sirianni GL, Pang KS. Organ clearance concepts: new perspectives on old principles. J Pharmaco-kinet Biopharm 1997; 25: 449-470.
31. Liu L, Pang KS. An integrated approach to model hepatic drug clearance. Eur J Pharm Sci 2006; 29: 215-230.
32. Cummins CL, Mangravite LM, Benet LZ. Characterizing the expression of CYP3A4 and efflux transporters (P-gp, MRP1, and MRP2) in CYP3A4-transfected Caco-2 cells after induction with sodium butyrate and the phorbol ester 12-o-tetradecanoylphorbol-13-acetate. Pharm Res 2001; 18: 1102-1109.
33. Schmiedlin-Ren P, Thummel KE, Fisher JM, Paine MF, Watkins PB. Induction of CYP3A4 by 1α, 25-dihydroxyvitamin D3 is human cell line-specific and is unlikely to involve pregnane X receptor. Drug Metab Dispos 2001; 29: 1446-1453.
34. Lin JH, Chiba M, Baillie TA. Is the role of the small intestine in first-pass metabolism overemphasized? Pharmacol Rev 1999; 51: 135-158.
35. Wacher VJ, Salphati L, Benet LZ. Active secretion and enterocytic drug metabolism barriers to drug absorption. Adv Drug Deliv Rev 2001; 46: 89-102. (Pubitemid 33653416)
36. Johnson BM, Charman WN, Porter CJH. The impact of P-glycoprotein efflux on enterocyte residence time and enterocyte-based metabolism of verapamil. J Pharm Pharmacol 2001; 53: 1611-1619.
37. Johnson BM, Chen W, Borchardt RT, Charman WN, Porter CJH. A kinetic evaluation of the absorption, efflux, and metabolism of verapamil in the autoperfused rat jejunum. J Pharmacol Exp Ther 2003; 305: 151-158.
38. Tam D, Tirona RG, Pang KS. Segmental intestinal transporters and metabolic enzymes on intestinal drug absorption. Drug Metab Dispos 2003; 31: 373-383.
39. Eagling VA, Wiltshire H, Whitcombe IW, Back DJ. Cyp3A4-mediated hepatic metabolism of the HIV-1 protease inhibitor saquinavir in vitro. Xenobiotica 2002; 32: 1-17.
40. Fitzsimmons ME, Collins JM. Selective biotrans-formation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4: potential contribution to high first-pass metabolism. Drug Metab Dispos 1997; 25: 256-266.
41. Foger F, Kafedjiiski K, Hoyer H, Loretz B, Bernkop-Schnurch A. Enhanced transport of P-glycoprotein substrate saquinavir in presence of thiolated chitosan. J Drug Target 2007; 15: 132-139.