Kinetics of cellular retention during caco-2 permeation experiments: Role of lysosomal sequestration and impact on permeability estimates

Journal of Pharmacology and Experimental Therapeutics

Volumn 328, Issue 3, 2009, Pages 882-892

  Heikkinen, Aki T ^a,b   Mönkkönen, Jukka ^a,b   Korjamo, Timo ^c  

^a UNIVERSITY OF EASTERN FINLAND   (Finland)

^b Biocenter Kuopio   (Finland)

^c Novamass Ltd   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

IBUPROFEN; PROPRANOLOL; TESTOSTERONE;

ARTICLE; CELL STRAIN CACO 2; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG BINDING; DRUG DISTRIBUTION; DRUG METABOLISM; DRUG PENETRATION; DRUG RETENTION; HUMAN; HUMAN CELL; LYSOSOME; MONOLAYER CULTURE; PKA; PRIORITY JOURNAL;

BIOLOGICAL TRANSPORT; CACO-2 CELLS; CELL MEMBRANE PERMEABILITY; CYTOSOL; HUMANS; IBUPROFEN; KINETICS; LYSOSOMES; MACROLIDES; MODELS, BIOLOGICAL; PROPRANOLOL; TESTOSTERONE;

EID: 62449161855     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.108.145797     Document Type: Article

References (29)

1. Artursson P, Palm K, and Luthman K (2001) Caco-2 monolayers in experimental and theoretical predictions of drug transport. Adv Drug Deliv Rev 46:27-43.
2. Asokan A and Cho MJ (2002) Exploitation of intracellular pH gradients in the cellular delivery of macromolecules. J Pharm Sci 91:903-913.
3. Bentz J, Tran TT, Polli JW, Ayrton A, and Ellens H (2005) The steady-state Michaelis-Menten analysis of P-glycoprotein mediated transport through a confluent cell monolayer cannot predict the correct Michaelis constant Km. Pharm Res 22:1667-1677.
4. Bowman EJ, Siebers A, and Altendorf K (1988) Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells. Proc Natl Acad Sci USA 85:7972-7976.
5. Duvvuri M, Gong Y, Chatterji D, and Krise JP (2004) Weak base permeability characteristics influence the intracellular sequestration site in the multidrugresistant human leukemic cell line HL-60. J Biol Chem 279:32367-32372.
6. Duvvuri M and Krise JP (2005) Intracellular drug sequestration events associated with the emergence of multidrug resistance: a mechanistic review. Front Biosci 10:1499-1509.
7. Engman HA, Lennernäs H, Taipalensuu J, Otter C, Leidvik B, and Artursson P (2001) CYP3A4, CYP3A5, and MDR1 in human small and large, intestinal cell lines suitable for drug transport studies. J Pharm Sci 90:1736-1751.
8. Fisher JM, Wrighton SA, Watkins PB, Schmiedlin-Ren P, Calamia JC, Shen DD, Kunze KL, and Thummel KE (1999) First-pass midazolam metabolism catalyzed by lalpha,25-dihydroxy vitamin D3-modified Caco-2 cell monolayers. J Pharmacol Exp Ther 289:1134-1142.
9. Hayeshi R, Masimirembwa C, Mukanganyama S, and Ungell AL (2008) Lysosomal trapping of amodiaquine: impact on transport across intestinal epithelia models. Biopharm Drug Dispos 29:324-334.
10. Ho NFH, Raub TJ, Burton PS, Barsuhn CL, Adson A, Audus KL, and Borchardt RT (1999) Quantitative approaches to delineate passive transport, mechanisms in cell culture monolayers, in Transport Processes in Pharmaceutical Systems (Amidon GL, Lee PI, and Topp EM eds) pp 219-316, Marcel Dekker Incorporated, New York.
11. Kaufmann AM and Krise JP (2007) Lysosomal sequestration of aminie-containing drugs: analysis and therapeutic implications. J Pharm Sci 96:729-746.
12. Korjamo T, Heikkinen AT, Waltari P, and Mönkkdnen J (2008) The asymmetry of the unstirred water layer in permeability experiments. Pharm Res 25:1714-1722.
13. Korjamo T, Honkakoski P, Toppinen MR, Niva S, Reinisalo M, Palmgrén JJ, and Mönkkönen J (2005) Absorption properties and P-glycoprotein activity of modified Caco-2 cell lines. Eur J Pharm, Sci 26:266-279.
14. Korjamo T, Kemiläinen H, Heikkinen AT, and Monkkdnen J (2007) Decrease ni intracellular concentration causes the shift in km value of efflux pump substrates. Drug Metab Dispos 35:1574-1579.
15. Korjamo T, Mönkkönen J, Uusitalo J, Turpeinen M, Pelkonen O, and Honkakoski P (2006) Metabolic and efflux properties of caco-2 cells stably transfected with nuclear receptors. Pharm Res 23:1991-2001.
16. Linnankoski J, Ranta VP, Yliperttula M, and Urtti A (2008) Passive oral drug absorption can be predicted more reliably by experimental than computational models: fact or myth. Eur J Pharm Sci 34:129-139.
17. Ohkuma S and Poole B (1981) Cytoplasmic vacuolation of mouse peritoneal macrophages and the uptake into lysosomes of weakly basic substances. J Cell Biol 90:656-664.
18. Östh K, Gråsjö J, and Björk E (2002) A new method for drug transport studies on pig nasal mucosa using a horizontal ussmg chamber. J Pharm Sci 91:1259-1273.
19. Palm K, Luthman K, Ros J, Grasjo J, and Artursson P (1999) Effect of molecular charge on intestinal epithelial drug transport: pH-dependent transport of cat ionic drugs. J Pharmacol Exp Ther 291:435-443.
20. Palmgrén JJ, Mönkkönen J, Korjamo T, Hassinen A, and Auriola S (2006) Drug adsorption to plastic containers and retention of drugs in cultured cells under in vitro conditions. Eur J Pharm Biopharm 64:369-378.
21. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, and Serabjit-Singh CS (2001) Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther 299:620-628.
22. Poole B and Ohkuma S (1981) Effect of weak bases on the intralysosomal pH in mouse peritoneal macrophages. J Cell Biol 90:665-669.
23. Prueksaritanont T, Gorham LM, Hochman JH, Tran LO, and Vyas KP (1996) Comparative studies of drug-metabolizing enzymes in dog, monkey, and human small intestines, and in caco-2 cells. Drug Metab Dispos 24:634-642.
24. Sawada GA, Barsuhn CL, Lutzke BS, Houghton ME, Padbury GE, Ho NF, and Raub TJ (1999) Increased lipophilicity and subsequent cell partitioning decrease passive transcellular diffusion of novel, highly lipophilic antioxidants. J Pharmacol Exp Ther 288:1317-1326.
25. Simons K and van Meer G (1988) Lipid sorting in epithelial cells. Biochemistry 27:6197-6202.
26. Sun H and Pang KS (2008) Permeability, transport, and metabolism of solutes in caco-2 cell monolayers: a theoretical study. Drug Metab Dispos 36:102-123.
27. Tran TT, Mittal A, Gales T, Maleeff B, Aldinger T, Polli JW, Ayrton A, Ellens H, and Bentz J (2004) Exact kinetic analysis of passive transport across a polarized confluent MDCK cell monolayer modeled as a single barrier. J Pharm Sci 93: 2108-2123.
28. (+:)-ATPase, hihibits acidification and protein degradation in lysosomes of cultured cells. J Biol Chem, 266:17707-17712.
29. Youdim KA, Avdeef A, and Abbott NJ (2003) In vitro trans-monolayer permeability calculations: often forgotten assumptions. Drug Discov Today 8:997-1003.