Evaluation of Drug Biliary Excretion Using Sandwich-Cultured Human Hepatocytes

Overview

Journal Eur J Drug Metab Pharmacokinet

Date 2018 Sep 1

PMID 30167999

Citations 4

Authors

Olivier Fardel

Amelie Moreau

Marc Le Vee

Claire Denizot

Yannick Parmentier

Affiliations

Soon will be listed here.

Abstract

Evaluation of hepatobiliary transport of drugs is an important challenge, notably during the development of new molecular identities. In this context, sandwich-cultured human hepatocytes (SCHH) have been proposed as an interesting and integrated tool for predicting in vitro biliary excretion of drugs. The present review was therefore designed to summarize key findings about SCHH, including their establishment, their main functional features and their use for the determination of canalicular transport and the prediction of in vivo biliary clearance and hepatobiliary excretion-related drug-drug interactions. Reviewed data highlight the fact that SCHH represent an original and probably unique holistic in vitro approach to predict biliary clearance in humans, through taking into account sinusoidal drug uptake, passive drug diffusion, drug metabolism and sinusoidal and canalicular drug efflux. Limits and proposed refinements for SCHH-based analysis of drug biliary excretion, as well as putative human alternative in vitro models to SCHH are also discussed.

Citing Articles

Optimization of extracellular matrix for primary human hepatocyte cultures using mixed collagen-Matrigel matrices.

Seidemann L, Prinz S, Scherbel J, Gotz C, Seehofer D, Damm G EXCLI J. 2023; 22:12-34.

PMID: 36660192 PMC: 9837384. DOI: 10.17179/excli2022-5459.

Analyzing the metabolic fate of oral administration drugs: A review and state-of-the-art roadmap.

Liu L, Liu Y, Zhou X, Xu Z, Zhang Y, Ji L Front Pharmacol. 2022; 13:962718.

PMID: 36278150 PMC: 9585159. DOI: 10.3389/fphar.2022.962718.

Contribution of Humanized Liver Chimeric Mice to the Study of Human Hepatic Drug Transporters: State of the Art and Perspectives.

Zerdoug A, Le Vee M, Uehara S, Lopez B, Chesne C, Suemizu H Eur J Drug Metab Pharmacokinet. 2022; 47(5):621-637.

PMID: 35793042 DOI: 10.1007/s13318-022-00782-9.

Influence of Proteome Profiles and Intracellular Drug Exposure on Differences in CYP Activity in Donor-Matched Human Liver Microsomes and Hepatocytes.

Wegler C, Matsson P, Krogstad V, Urdzik J, Christensen H, Andersson T Mol Pharm. 2021; 18(4):1792-1805.

PMID: 33739838 PMC: 8041379. DOI: 10.1021/acs.molpharmaceut.1c00053.

References

Herrine S, Choudhary C . Severe hepatotoxicity associated with troglitazone. Ann Intern Med. 1999; 130(2):163-4. DOI: 10.7326/0003-4819-130-2-199901190-00021. View

Liu X, LeCluyse E, Brouwer K, Lightfoot R, Lee J, Brouwer K . Use of Ca2+ modulation to evaluate biliary excretion in sandwich-cultured rat hepatocytes. J Pharmacol Exp Ther. 1999; 289(3):1592-9. View

Liu X, Chism J, LeCluyse E, Brouwer K, Brouwer K . Correlation of biliary excretion in sandwich-cultured rat hepatocytes and in vivo in rats. Drug Metab Dispos. 1999; 27(6):637-44. View

Liu X, LeCluyse E, Brouwer K, Gan L, Lemasters J, Stieger B . Biliary excretion in primary rat hepatocytes cultured in a collagen-sandwich configuration. Am J Physiol. 1999; 277(1):G12-21. DOI: 10.1152/ajpgi.1999.277.1.G12. View

Bolder U, Trang N, Hagey L, Schteingart C, Cerre C, Elferink R . Sulindac is excreted into bile by a canalicular bile salt pump and undergoes a cholehepatic circulation in rats. Gastroenterology. 1999; 117(4):962-71. DOI: 10.1016/s0016-5085(99)70356-2. View

Lecluyse E, Madan A, Hamilton G, Carroll K, DeHaan R, Parkinson A . Expression and regulation of cytochrome P450 enzymes in primary cultures of human hepatocytes. J Biochem Mol Toxicol. 2000; 14(4):177-88. DOI: 10.1002/(sici)1099-0461(2000)14:4<177::aid-jbt1>3.0.co;2-4. View

Pou L, Brunet M, Cantarell C, Vidal E, Oppenheimer F, Monforte V . Mycophenolic acid plasma concentrations: influence of comedication. Ther Drug Monit. 2001; 23(1):35-8. DOI: 10.1097/00007691-200102000-00007. View

Fattinger K, Funk C, Pantze M, Weber C, Reichen J, Stieger B . The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. Clin Pharmacol Ther. 2001; 69(4):223-31. DOI: 10.1067/mcp.2001.114667. View

Funk C, Pantze M, Jehle L, Ponelle C, Scheuermann G, Lazendic M . Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export of bile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and the inhibition of the canalicular bile.... Toxicology. 2001; 167(1):83-98. DOI: 10.1016/s0300-483x(01)00460-7. View

10.

Annaert P, Turncliff R, Booth C, Thakker D, Brouwer K . P-glycoprotein-mediated in vitro biliary excretion in sandwich-cultured rat hepatocytes. Drug Metab Dispos. 2001; 29(10):1277-83. View

11.

Roberts M, Magnusson B, Burczynski F, Weiss M . Enterohepatic circulation: physiological, pharmacokinetic and clinical implications. Clin Pharmacokinet. 2002; 41(10):751-90. DOI: 10.2165/00003088-200241100-00005. View

12.

Lau Y, Sapidou E, Cui X, White R, Cheng K . Development of a novel in vitro model to predict hepatic clearance using fresh, cryopreserved, and sandwich-cultured hepatocytes. Drug Metab Dispos. 2002; 30(12):1446-54. DOI: 10.1124/dmd.30.12.1446. View

13.

Pinto A, Cummings O, Chalasani N . Severe but reversible cholestatic liver injury after pioglitazone therapy. Ann Intern Med. 2002; 137(10):857. DOI: 10.7326/0003-4819-137-10-200211190-00023. View

14.

Faber K, Muller M, Jansen P . Drug transport proteins in the liver. Adv Drug Deliv Rev. 2003; 55(1):107-24. DOI: 10.1016/s0169-409x(02)00173-4. View

15.

Sulkowski M . Hepatotoxicity associated with antiretroviral therapy containing HIV-1 protease inhibitors. Semin Liver Dis. 2003; 23(2):183-94. DOI: 10.1055/s-2003-39949. View

16.

Kostrubsky V, Strom S, Hanson J, Urda E, Rose K, Burliegh J . Evaluation of hepatotoxic potential of drugs by inhibition of bile-acid transport in cultured primary human hepatocytes and intact rats. Toxicol Sci. 2003; 76(1):220-8. DOI: 10.1093/toxsci/kfg217. View

17.

Chandra P, Brouwer K . The complexities of hepatic drug transport: current knowledge and emerging concepts. Pharm Res. 2004; 21(5):719-35. DOI: 10.1023/b:pham.0000026420.79421.8f. View

18.

Turncliff R, Meier P, Brouwer K . Effect of dexamethasone treatment on the expression and function of transport proteins in sandwich-cultured rat hepatocytes. Drug Metab Dispos. 2004; 32(8):834-9. DOI: 10.1124/dmd.32.8.834. View

19.

Hoffmaster K, Turncliff R, LeCluyse E, Kim R, Meier P, Brouwer K . P-glycoprotein expression, localization, and function in sandwich-cultured primary rat and human hepatocytes: relevance to the hepatobiliary disposition of a model opioid peptide. Pharm Res. 2004; 21(7):1294-302. DOI: 10.1023/b:pham.0000033018.97745.0d. View

20.

Kemp D, Zamek-Gliszczynski M, Brouwer K . Xenobiotics inhibit hepatic uptake and biliary excretion of taurocholate in rat hepatocytes. Toxicol Sci. 2004; 83(2):207-14. DOI: 10.1093/toxsci/kfi020. View