A comprehensive evaluation of metabolic activity and intrinsic clearance in suspensions and monolayer cultures of cryopreserved primary human hepatocytes

Journal of Pharmaceutical Sciences

Volumn 101, Issue 10, 2012, Pages 3989-4002

  Smith, Cornelia M ^a   Nolan, Christina K ^a   Edwards, Manda A ^a   Hatfield, Jean B ^a   Stewart, Todd W ^a   Ferguson, Stephen S ^a   Lecluyse, Edward L ^a   Sahi, Jasminder ^a  

^a ADME/TOX Division of Life Technologies   (United States)

Author keywords

Clearance; CYP enzymes; Cytochrome P450; Flavin monooxygenases (FMO); Hepatic clearance; Hepatic metabolism; Hepatocytes; Metabolic clearance

Indexed keywords

7 ETHOXYCOUMARIN; AMFEBUTAMONE; BENZYDAMINE; CYTOCHROME P450 1A2; CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A; DEXAMETHASONE; DEXTROMETHORPHAN; DIAZEPAM; DICLOFENAC; DIMETHYLANILINE MONOOXYGENASE; GLUCURONOSYLTRANSFERASE; MEPHENYTOIN; MIDAZOLAM; PACLITAXEL; PARACETAMOL; PHENACETIN; SULFOTRANSFERASE; TESTOSTERONE; UMBELLIFERONE;

ADULT; AGED; ARTICLE; CELL ADHESION; CELL METABOLISM; CLINICAL EVALUATION; CONTROLLED STUDY; CRYOPRESERVATION; DONOR; DRUG CLEARANCE; ENZYME ACTIVITY; ENZYME INACTIVATION; ENZYME STABILITY; FEMALE; HUMAN; HUMAN CELL; LIVER CELL CULTURE; MALE; MONOLAYER CULTURE; STATISTICAL SIGNIFICANCE; SUSPENSION;

EID: 84862239072     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.23262     Document Type: Article

References (33)

1. Kola I, Landis J. 2004. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3(8):711-715.
2. Tamimi NA, Ellis P. 2009. Drug development: From concept to marketing! Nephron Clin Pract 113(3):c125-c131.
3. USFDA. 2006. Draft guidance for industry: Drug interaction studies-Study design, data analysis, and implications for dosing and labeling. Silver Spring, Maryland: USFDA.
4. Jones HM, Houston JB. 2004. Substrate depletion approach for determining in vitro metabolic clearance: Time dependencies in hepatocyte and microsomal incubations. Drug Metab Dispos 32(9):973-982.
5. 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(11):1350-1359.
6. Masimirembwa CM, Bredberg U, Andersson TB. 2003. Metabolic stability for drug discovery and development: Pharmacokinetic and biochemical challenges. Clin Pharmacokinet 42(6):515-528.
7. Houston JB, Carlile DJ. 1997. Prediction of hepatic clearance from microsomes, hepatocytes, and liver slices. Drug Metab Rev 29(4):891-922.
8. Ito K, Houston JB. 2004. Comparison of the use of liver models for predicting drug clearance using in vitro kinetic data from hepatic microsomes and isolated hepatocytes. Pharm Res 21(5):785-792.
9. Nagilla R, Frank KA, Jolivette LJ, Ward KW. 2006. Investigation of the utility of published in vitro intrinsic clearance data for prediction of in vivo clearance. J Pharmacol Toxicol Methods 53(2):106-116.
10. Hewitt NJ, Lechon MJ, Houston JB, Hallifax D, Brown HS, Maurel P, Kenna JG, Gustavsson L, Lohmann C, Skonberg C, Guillouzo A, Tuschl G, Li AP, LeCluyse E, Groothuis GM, Hengstler JG. 2007. Primary hepatocytes: Current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. Drug Metab Rev 39(1):159-234.
11. Li AP, Lu C, Brent JA, Pham C, Fackett A, Ruegg CE, Silber PM. 1999. Cryopreserved human hepatocytes: Characterization of drug-metabolizing enzyme activities and applications in higher throughput screening assays for hepatotoxicity, metabolic stability, and drug-drug interaction potential. Chem Biol Interact 121(1):17-35.
12. Steinberg P, Fischer T, Kiulies S, Biefang K, Platt KL, Oesch F, Bottger T, Bulitta C, Kempf P, Hengstler J. 1999. Drug metabolizing capacity of cryopreserved human, rat, and mouse liver parenchymal cells in suspension. Drug Metab Dispos 27(12):1415-1422.
13. Laine R. 2008. Metabolic stability: Main enzymes involved and best tools to assess it. Curr Drug Metab 9(9):921-927.
14. Jouin D, Blanchard N, Alexandre E, Delobel F, David-Pierson P, Lave T, Jaeck D, Richert L, Coassolo P. 2006. Cryopreserved human hepatocytes in suspension are a convenient high throughput tool for the prediction of metabolic clearance. Eur J Pharm Biopharm 63(3):347-355.
15. LeCluyse EL, Alexandre E, Hamilton GA, Viollon-Abadie C, Coon DJ, Jolley S, Richert L. 2005. Isolation and culture of primary human hepatocytes. Methods Mol Biol 290:207-229.
16. Alexandre E, Viollon-Abadie C, David P, Gandillet A, Coassolo P, Heyd B, Mantion G, Wolf P, Bachellier P, Jaeck D, Richert L. 2002. Cryopreservation of adult human hepatocytes obtained from resected liver biopsies. Cryobiology 44(2):103-113.
17. Gomez-Lechon MJ, Lahoz A, Jimenez N, Vicente Castell J, Donato MT. 2006. Cryopreservation of rat, dog and human hepatocytes: Influence of preculture and cryoprotectants on recovery, cytochrome P450 activities and induction upon thawing. Xenobiotica 36(6):457-472.
18. Madan A, DeHaan R, Mudra D, Carroll K, LeCluyse E, Parkinson A. 1999. Effect of cryopreservation on cytochrome P-450 enzyme induction in cultured rat hepatocytes. Drug Metab Dispos 27(3):327-335.
19. Lau YY, Sapidou E, Cui X, White RE, Cheng KC. 2002. Development of a novel in vitro model to predict hepatic clearance using fresh, cryopreserved, and sandwich-cultured hepatocytes. Drug Metab Dispos 30(12):1446-1454.
20. McGinnity DF, Soars MG, Urbanowicz RA, Riley RJ. 2004. Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance. Drug Metab Dispos 32(11):1247-1253.
21. Gebhardt R, Hengstler JG, Muller D, Glockner R, Buenning P, Laube B, Schmelzer E, Ullrich M, Utesch D, Hewitt N, Ringel M, Hilz BR, Bader A, Langsch A, Koose T, Burger HJ, Maas J, Oesch F. 2003. New hepatocyte in vitro systems for drug metabolism: Metabolic capacity and recommendations for application in basic research and drug development, standard operation procedures. Drug Metab Rev 35(2-3):145-213.
22. Hewitt NJ, Buhring KU, Dasenbrock J, Haunschild J, Ladstetter B, Utesch D. 2001. Studies comparing in vivo:in vitro metabolism of three pharmaceutical compounds in rat, dog, monkey, and human using cryopreserved hepatocytes, microsomes, and collagen gel immobilized hepatocyte cultures. Drug Metab Dispos 29(7):1042-1050.
23. Hallifax D, Galetin A, Houston JB. 2008. Prediction of metabolic clearance using fresh human hepatocytes: Comparison with cryopreserved hepatocytes and hepatic microsomes for five benzodiazepines. Xenobiotica 38(4):353-367.
24. Floby E, Johansson J, Hoogstraate J, Hewitt NJ, Hill J, Sohlenius-Sternbeck AK. 2009. Comparison of intrinsic metabolic clearance in fresh and cryopreserved human hepatocytes. Xenobiotica 39(9):656-662.
25. Domanski TL, He YA, Khan KK, Roussel F, Wang Q, Halpert JR. 2001. Phenylalanine and tryptophan scanning mutagenesis of CYP3A4 substrate recognition site residues and effect on substrate oxidation and cooperativity. Biochemistry 40(34):10150-10160.
26. Korzekwa KR, Krishnamachary N, Shou M, Ogai A, Parise RA, Rettie AE, Gonzalez FJ, Tracy TS. 1998. Evaluation of atypical cytochrome P450 kinetics with two-substrate models: Evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry 37(12):4137-4147.
27. Hewitt NJ, Utesch D. 2004. Cryopreserved rat, dog and monkey hepatocytes: Measurement of drug metabolizing enzymes in suspensions and cultures. Hum Exp Toxicol 23(6):307-316.
28. Griffin SJ, Houston JB. 2005. Prediction of in vitro intrinsic clearance from hepatocytes: Comparison of suspensions and monolayer cultures. Drug Metab Dispos 33(1):115-120.
29. Stringer R, Nicklin PL, Houston JB. 2008. Reliability of human cryopreserved hepatocytes and liver microsomes as in vitro systems to predict metabolic clearance. Xenobiotica 38(10):1313-1329.
30. Treijtel N, Barendregt A, Freidig AP, Blaauboer BJ, van Eijkeren JC. 2004. Modeling the in vitro intrinsic clearance of the slowly metabolized compound tolbutamide determined in sandwich-cultured rat hepatocytes. Drug Metab Dispos 32(8):884-891.
31. Treijtel N, van Helvoort H, Barendregt A, Blaauboer BJ, van Eijkeren JC. 2005. The use of sandwich-cultured rat hepatocytes to determine the intrinsic clearance of compounds with different extraction ratios: 7-Ethoxycoumarin and warfarin. Drug Metab Dispos 33(9):1325-1332.
32. Skett P. 1994. Problems in using isolated and cultured hepatocytes for xenobiotic metabolism/metabolism-based toxicity testing-Solutions? Toxicol In Vitro 8(3):491-504.
33. Li AP. 2007. Human hepatocytes: Isolation, cryopreservation and applications in drug development. Chem Biol Interact 168(1):16-29.