Determination of intracellular unbound concentrations and subcellular localization of drugs in rat sandwich-cultured hepatocytes compared with liver tissue

Drug Metabolism and Disposition

Volumn 41, Issue 11, 2013, Pages 1949-1956

  Pfeifer, Nathan D ^a   Harris, Kevin B ^a   Zhixia, Yan G ^a   Brouwer, Kim L R ^a  

^a UNC Hamner Institute for Drug Safety Sciences   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,5 BIS(4 AMIDINOPHENYL)FURAN; RITONAVIR; ROSUVASTATIN;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CELL COMPARTMENTALIZATION; CELL FRACTIONATION; CELL LYSATE; CELLULAR DISTRIBUTION; CENTRIFUGATION; CONTROLLED STUDY; CYTOSOL; DRUG ACCUMULATION; DRUG BINDING; DRUG DISTRIBUTION; DRUG LIVER LEVEL; DRUG UPTAKE; EQUILIBRIUM DIALYSIS; LIQUID CHROMATOGRAPHY; LIVER CELL CULTURE; LIVER PARENCHYMA; LIVER PERFUSION; MALE; NONHUMAN; PREDICTION; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; RAT; TANDEM MASS SPECTROMETRY;

ANIMALS; CELLS, CULTURED; DRUG INTERACTIONS; HEPATOCYTES; LIVER; MALE; PHARMACEUTICAL PREPARATIONS; RATS; RATS, WISTAR; TISSUE DISTRIBUTION;

EID: 84886533717     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.113.052134     Document Type: Article

References (60)

1. Abe K, Bridges AS, Yue W, and Brouwer KLR (2008) In vitro biliary clearance of angiotensin II receptor blockers and 3-hydroxy-3-methylglutaryl- coenzyme A reductase inhibitors in sandwich-cultured rat hepatocytes: comparison with in vivo biliary clearance. J Pharmacol Exp Ther 326:983-990.
2. Annaert P, Ye ZW, Stieger B, and Augustijns P (2010) Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1. Xenobiotica 40:163-176.
3. Bow DA, Perry JL, Miller DS, Pritchard JB, and Brouwer KLR (2008) Localization of P-gp (Abcb1) and Mrp2 (Abcc2) in freshly isolated rat hepatocytes. Drug Metab Dispos 36: 198-202.
4. Brouwer KLR and Thurman RG (1996) Isolated perfused liver. Pharm Biotechnol 8:161-192.
5. Brown HS, Wilby AJ, Alder J, and Houston JB (2010) Comparative use of isolated hepatocytes and hepatic microsomes for cytochrome P450 inhibition studies: transporter-enzyme interplay. Drug Metab Dispos 38:2139-2146.
6. Burnside J and Schneider DL (1982) Characterization of the membrane proteins of rat liver lysosomes. Composition, enzyme activities and turnover. Biochem J 204:525-534.
7. Chen YJ, Huang SM, Liu CY, Yeh PH, and Tsai TH (2008) Hepatobiliary excretion and enterohepatic circulation of colchicine in rats. Int J Pharm 350:230-239.
8. Chu X, Korzekwa K, Elsby R, Fenner K, Galetin A, Lai Y, Matsson P, Moss A, Nagar S, and Rosania GR, et al.; International Transporter Consortium (2013) Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver. Clin Pharmacol Ther 94:126-141.
9. Denissen JF, Grabowski BA, Johnson MK, Buko AM, Kempf DJ, Thomas SB, and Surber BW (1997) Metabolism and disposition of the HIV-1 protease inhibitor ritonavir (ABT-538) in rats, dogs, and humans. Drug Metab Dispos 25:489-501.
10. Deshmukh SV and Harsch A (2011) Direct determination of the ratio of unbound fraction in plasma to unbound fraction in microsomal system (fu p/fu mic) for refined prediction of phase I mediated metabolic hepatic clearance. J Pharmacol Toxicol Methods 63:35-39.
11. Dollery CT (2013) Intracellular drug concentrations. Clin Pharmacol Ther 93:263-266.
12. Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KLR, 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.
13. Gong Y, Zhao Z, McConn DJ, Beaudet B, Tallman M, Speake JD, Ignar DM, and Krise JP (2007) Lysosomes contribute to anomalous pharmacokinetic behavior of melanocortin-4 receptor agonists. Pharm Res 24:1138-1144.
14. Griffin L, Annaert P, and Brouwer KLR (2011) Influence of drug transport proteins on the pharmacokinetics and drug interactions of HIV protease inhibitors. J Pharm Sci 100: 3636-3654.
15. Gunawan BK and Kaplowitz N (2007) Mechanisms of drug-induced liver disease. Clin Liver Dis 11:459-475.
16. Gupta A, Chatelain P, Massingham R, Jonsson EN, and Hammarlund-Udenaes M (2006) Brain distribution of cetirizine enantiomers: comparison of three different tissue-to-plasma partition coefficients: K(p), K(p,u), and K(p,uu). Drug Metab Dispos 34:318-323.
17. Gutmann H, Fricker G, Drewe J, Toeroek M, and Miller DS (1999) Interactions of HIV protease inhibitors with ATP-dependent drug export proteins. Mol Pharmacol 56:383-389.
18. Hammarlund-Udenaes M, Fridén M, Syvänen S, and Gupta A (2008) On the rate and extent of drug delivery to the brain. Pharm Res 25:1737-1750.
19. Herbette L, Katz AM, and Sturtevant JM (1983) Comparisons of the interaction of propranolol and timolol with model and biological membrane systems. Mol Pharmacol 24:259-269.
20. Igari Y, Sugiyama Y, Awazu S, and Hanano M (1981) Interspecies difference in drug protein binding-temperature and protein concentration dependency: effect on calculation of effective protein fraction. J Pharm Sci 70:1049-1053.
21. Jones HM, Barton HA, Lai Y, Bi YA, Kimoto E, Kempshall S, Tate SC, El-Kattan A, Houston JB, and Galetin A, et al. (2012) Mechanistic pharmacokinetic modeling for the prediction of transporter-mediated disposition in humans from sandwich culture human hepatocyte data. Drug Metab Dispos 40:1007-1017.
22. Kalvass JC, Maurer TS, and Pollack GM (2007) Use of plasma and brain unbound fractions to assess the extent of brain distribution of 34 drugs: comparison of unbound concentration ratios to in vivo p-glycoprotein efflux ratios. Drug Metab Dispos 35:660-666.
23. Kodama H, Kodama Y, Shinozawa S, Kanemaru R, Todaka K, and Mitsuyama Y (1999) Temperature effect on serum protein binding kinetics of phenytoin in monotherapy patients with epilepsy. Eur J Pharm Biopharm 47:295-298.
24. Kudo N, Sakai A, Mitsumoto A, Hibino Y, Tsuda T, and Kawashima Y (2007) Tissue distribution and hepatic subcellular distribution of perfluorooctanoic acid at low dose are different from those at high dose in rats. Biol Pharm Bull 30:1535-1540.
25. Labbe G, Pessayre D, and Fromenty B (2008) Drug-induced liver injury through mitochondrial dysfunction: mechanisms and detection during preclinical safety studies. Fundam Clin Pharmacol 22:335-353.
26. Lee JK and Brouwer KR (2010) Determination of intracellular volume of rat and human sandwich-cultured hepatocytes (Abstract ID 1595). Toxicol Sci 114:339.
27. Li N, Bi YA, Duignan DB, and Lai Y (2009) Quantitative expression profile of hepatobiliary transporters in sandwich cultured rat and human hepatocytes. Mol Pharm 6:1180-1189.
28. Liu X, Chen C, and Smith BJ (2008) Progress in brain penetration evaluation in drug discovery and development. J Pharmacol Exp Ther 325:349-356.
29. Liu XY, Yang Q, Kamo N, and Miyake J (2001) Effect of liposome type and membrane fluidity on drug-membrane partitioning analyzed by immobilized liposome chromatography. J Chromatogr A 913:123-131.
30. Mateus A, Matsson P, and Artursson P (2013) Rapid measurement of intracellular unbound drug concentrations. Mol Pharm 10:2467-2478.
31. Midgley I, Fitzpatrick K, Taylor LM, Houchen TL, Henderson SJ, Wright SJ, Cybulski ZR, John BA, McBurney A, and Boykin DW, et al. (2007) Pharmacokinetics and metabolism of the prodrug DB289 (2,5-bis[4-(N-methoxyamidino)phenyl]furan monomaleate) in rat and monkey and its conversion to the antiprotozoal/ antifungal drug DB75 (2,5-bis(4-guanylphenyl)furan dihydrochloride). Drug Metab Dispos 35:955-967.
32. Nezasa K, Higaki K, Matsumura T, Inazawa K, Hasegawa H, Nakano M, and Koike M (2002a) Liver-specific distribution of rosuvastatin in rats: comparison with pravastatin and simvastatin. Drug Metab Dispos 30:1158-1163.
33. Nezasa K, Higaki K, Takeuchi M, Nakano M, and Koike M (2003) Uptake of rosuvastatin by isolated rat hepatocytes: comparison with pravastatin. Xenobiotica 33:379-388.
34. Nezasa K, Takao A, Kimura K, Takaichi M, Inazawa K, and Koike M (2002b) Pharmacokinetics and disposition of rosuvastatin, a new 3-hydroxy-3- methylglutaryl coenzyme A reductase inhibitor, in rat. Xenobiotica 32:715-727.
35. Obach RS (1996) The importance of nonspecific binding in in vitro matrices, its impact on enzyme kinetic studies of drug metabolism reactions, and implications for in vitro-in vivo correlations. Drug Metab Dispos 24:1047-1049.
36. Obach RS (1999) Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: an examination of in vitro half-life approach and nonspecific binding to microsomes. Drug Metab Dispos 27:1350-1359.
37. Ockerman PA (1967) Glucose-6-phosphatase assay on microgram amounts of liver tissue. Clin Chim Acta 17:201-206.
38. Ohsumi Y, Ishikawa T, and Kato K (1983) A rapid and simplified method for the preparation of lysosomal membranes from rat liver. J Biochem 93:547-556.
39. Paine MF, Wang MZ, Generaux CN, Boykin DW, Wilson WD, De Koning HP, Olson CA, Pohlig G, Burri C, and Brun R, et al. (2010) Diamidines for human African trypanosomiasis. Curr Opin Investig Drugs 11:876-883.
40. Palmeira CM and Oliveira CR (1992) Partitioning and membrane disordering effects of dopamine antagonists: influence of lipid peroxidation, temperature, and drug concentration. Arch Biochem Biophys 295:161-171.
41. Parker AJ and Houston JB (2008) Rate-limiting steps in hepatic drug clearance: comparison of hepatocellular uptake and metabolism with microsomal metabolism of saquinavir, nelfinavir, and ritonavir. Drug Metab Dispos 36:1375-1384.
42. Pfeifer ND, Goss SL, Swift B, Ghibellini G, Ivanovic M, Heizer WD, Gangarosa LM, and Brouwer KLR (2013) Effect of ritonavir on (99m)Technetium- mebrofenin disposition in humans: a semi-PBPK modeling and in vitro approach to predict transporter-mediated DDIs. CPT Pharmacometrics Syst Pharmacol 2:e20.
43. Reasor MJ and Kacew S (2001) Drug-induced phospholipidosis: are there functional consequences? Exp Biol Med (Maywood) 226:825-830.
44. Rezk NL, White NR, Jennings SH, and Kashuba AD (2009) A novel LC-ESI-MS method for the simultaneous determination of etravirine, darunavir and ritonavir in human blood plasma. Talanta 79:1372-1378.
45. Rodgers T, Leahy D, and Rowland M (2005) Physiologically based pharmacokinetic modeling 1: predicting the tissue distribution of moderate-to-strong bases. J Pharm Sci 94:1259-1276.
46. Rodgers T and Rowland M (2006) Physiologically based pharmacokinetic modelling 2: predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions. J Pharm Sci 95:1238-1257.
47. Sato K, Mizuki Y, and Komuro S (2010) Consideration of reliable concentrations for prediction of change in enzyme activity by mechanism-based inactivation using physiologically-based pharmacokinetic model simulations. Drug Metab Pharmacokinet 25:335-342.
48. Shitara Y, Maeda K, Ikejiri K, Yoshida K, Horie T, and Sugiyama Y (2013) Clinical significance of organic anion transporting polypeptides (OATPs) in drug disposition: their roles in hepatic clearance and intestinal absorption. Biopharm Drug Dispos 34:45-78.
49. Smith DA, Di L, and Kerns EH (2010) The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery. Nat Rev Drug Discov 9:929-939.
50. Swift B, Pfeifer ND, and Brouwer KLR (2010) Sandwich-cultured hepatocytes: an in vitro model to evaluate hepatobiliary transporter-based drug interactions and hepatotoxicity. Drug Metab Rev 42:446-471.
51. Tchaparian EH, Houghton JS, Uyeda C, Grillo MP, and Jin L (2011) Effect of culture time on the basal expression levels of drug transporters in sandwich-cultured primary rat hepatocytes. Drug Metab Dispos 39:2387-2394.
52. Vourvahis M and Kashuba AD (2007) Mechanisms of pharmacokinetic and pharmacodynamic drug interactions associated with ritonavir-enhanced tipranavir. Pharmacotherapy 27:888-909.
53. Ward ES, Pollack GM, and Brouwer KLR (2000) Probenecid-associated alterations in valproic acid pharmacokinetics in rats: can in vivo disposition of valproate glucuronide be predicted from in vitro formation data? Drug Metab Dispos 28:1433-1439.
54. Watkins PB, Seligman PJ, Pears JS, Avigan MI, and Senior JR (2008) Using controlled clinical trials to learn more about acute drug-induced liver injury. Hepatology 48:1680-1689.
55. Yabe Y, Galetin A, and Houston JB (2011) Kinetic characterization of rat hepatic uptake of 16 actively transported drugs. Drug Metab Dispos 39:1808-1814.
56. Yamano K, Yamamoto K, Kotaki H, Sawada Y, and Iga T (1999) Quantitative prediction of metabolic inhibition of midazolam by itraconazole and ketoconazole in rats: implication of concentrative uptake of inhibitors into liver. Drug Metab Dispos 27:395-402.
57. Yan GZ, Brouwer KLR, Pollack GM, Wang MZ, Tidwell RR, Hall JE, and Paine MF (2011) Mechanisms underlying differences in systemic exposure of structurally similar active metabolites: comparison of two preclinical hepatic models. J Pharmacol Exp Ther 337: 503-512.
58. Zeitlinger MA, Derendorf H, Mouton JW, Cars O, Craig WA, Andes D, and Theuretzbacher U (2011) Protein binding: do we ever learn? Antimicrob Agents Chemother 55:3067-3074.
59. Zhang J, Zhou F, Lu M, Ji W, Niu F, Zha W, Wu X, Hao H, and Wang G (2012) Pharmacokinetics-pharmacology disconnection of herbal medicines and its potential solutions with cellular pharmacokinetic-pharmacodynamic strategy. Curr Drug Metab 13: 558-576.
60. Zhou F, Zhang J, Li P, Niu F, Wu X, Wang G, and Roberts MS (2011) Toward a new age of cellular pharmacokinetics in drug discovery. Drug Metab Rev 43:335-345.