Bridging in vitro and in vivo metabolism and transport of faldaprevir in human using a novel cocultured human hepatocyte system, hepatopac

Drug Metabolism and Disposition

Volumn 42, Issue 3, 2014, Pages 394-406

  Ramsden, Diane ^a   Tweedie, Donald J ^a   Chan, Tom S ^a   Taub, Mitchell E ^a   Li, Yongmei ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRAL AGENTS; BIOLOGICAL TRANSPORT; BIOTRANSFORMATION; CELLS, CULTURED; COCULTURE TECHNIQUES; CRYOPRESERVATION; CULTURE MEDIA; CYTOCHROME P-450 CYP3A; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG STABILITY; FEMALE; FIBROBLASTS; GLUCURONIDES; HEPATOCYTES; HUMANS; KINETICS; LIVER; METABOLIC CLEARANCE RATE; MOLECULAR STRUCTURE; OLIGOPEPTIDES; ORGANIC ANION TRANSPORTERS; SODIUM; THIAZOLES;

EID: 84893860634     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.113.055897     Document Type: Article

References (33)

1. Barter ZE, Bayliss MK, Beaune PH, Boobis AR, Carlile DJ, Edwards RJ, Houston JB, Lake BG, Lipscomb JC, and Pelkonen OR, et al. (2007) Scaling factors for the extrapolation of in vivo metabolic drug clearance from in vitro data: reaching a consensus on values of human microsomal protein and hepatocellularity per gram of liver. Curr Drug Metab 8: 33-45.
2. Bow DA, Perry JL, Miller DS, Pritchard JB, and Brouwer KL (2008) Localization of P-gp (Abcb1) and Mrp2 (Abcc2) in freshly isolated rat hepatocytes. Drug Metab Dispos 36: 198-202.
3. Brouwer KL, Keppler D, Hoffmaster KA, Bow DA, Cheng Y, Lai Y, Palm JE, Stieger B, and Evers R; International Transporter Consortium (2013) In vitro methods to support transporter evaluation in drug discovery and development. Clin Pharmacol Ther 94: 95-112.
4. Chan TS, Yu H, Moore A, Kehtani SR, and Tweedie DJ (2013) Meeting the challenge of predicting hepatic clearance of compounds slowly metabolized by cytochrome P450 using a novel hepatocyte model, HepatoPac. Drug Metab Dispos 41:2024-2032.
5. Chen LZ, Rose P, Mao Y, Yong CL, St. George R, Huang F, Latli B, Mandarino D, and Li Y (2014) Steady-state disposition of the hepatitis C NS3/NS4 protease inhibitor faldaprevir in healthy male subjects. Antimicrob Agents Chemother, in press.
6. 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.
7. Davies B and Morris T (1993) Physiological parameters in laboratory animals and humans. Pharm Res 10:1093-1095.
8. Duan J, Yong CL, Garneau M, Amad M, Bolger G, De Marte J, Montpetit H, Otis F, Jutras M, and Rhéaume M, et al. (2012) Cross-species absorption, metabolism, distribution and pharmacokinetics of BI 201335, a potent HCV genotype 1 NS3/4A protease inhibitor. Xenobiotica 42:164-172.
9. European Medicines Agency (2012) Guideline on the Investigation of Drug Interactions, EMA/ CHMP/EWP/125211/2010, European Medicines Agency, London, UK. [http://www.ema. europa.eu/docs/en-GB/document-library/Scientific-guideline/ 2012/07/WC500129606.pdf (Accessed on Dec. 16, 2013)]
10. Food and Drug Administration (2012) Draft Guidance for Industry: Drug Interaction Studies- Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations, Draft, Food and Drug Administration, Silver Spring, MD. [http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/ucm292362.pdf (Accessed on Dec. 16, 2013)].
11. Ghibellini G, Leslie EM, and Brouwer KL (2006) Methods to evaluate biliary excretion of drugs in humans: an updated review. Mol Pharm 3:198-211.
12. Ho RH, Tirona RG, Leake BF, Glaeser H, Lee W, Lemke CJ, Wang Y, and Kim RB (2006) Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology 130:1793-1806.
13. Houston JB and Carlile DJ (1997) Prediction of hepatic clearance from microsomes, hepatocytes, and liver slices. Drug Metab Rev 29:891-922.
14. Khetani SR and Bhatia SN (2008) Microscale culture of human liver cells for drug development. Nat Biotechnol 26:120-126.
15. Khetani SR, Kanchagar C, Ukairo O, Krzyzewski S, Moore A, Shi J, Aoyama S, Aleo M, and Will Y (2013) Use of micropatterned cocultures to detect compounds that cause druginduced liver injury in humans. Toxicol Sci 132:107-117.
16. Kiser JJ, Burton JR, Jr, and Everson GT (2013) Drug-drug interactions during antiviral therapy for chronic hepatitis C. Nat Rev Gastroenterol Hepatol 10:596-606.
17. Li Y, Zhou J, Ramsden D, Taub ME, O'Brien D, Xu J, Busacca CA, Gonnella N, and Tweedie DJ (2014) Enzyme-transporter interplay in the formation and clearance of abundant metabolites of faldaprevir found in excreta but not in circulation. Drug Metab Dispos 42: 384-393.
18. Mita S, Suzuki H, Akita H, Hayashi H, Onuki R, Hofmann AF, and Sugiyama Y (2006) Inhibition of bile acid transport across Na+/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs. Drug Metab Dispos 34:1575-1581.
19. Manns MP, Bourlière M, Benhamou Y, Pol S, Bonacini M, Trepo C, Wright D, Berg T, Calleja JL, and White PW, et al. (2011) Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection. J Hepatol 54: 1114-1122.
20. Nadanaciva S, Lu S, Gebhard DF, Jessen BA, Pennie WD, and Will Y (2011) A high content screening assay for identifying lysosomotropic compounds. Toxicol In Vitro 25:715-723.
21. Nagar S and Korzekwa K (2012) Commentary: nonspecific protein binding versus membrane partitioning: it is not just semantics. Drug Metab Dispos 40:1649-1652.
22. Poulin P, Hop CE, Ho Q, Halladay JS, Haddad S, and Kenny JR (2012) Comparative assessment of in vitro-in vivo extrapolation methods used for predicting hepatic metabolic clearance of drugs. J Pharm Sci 101:4308-4326.
23. Ramsden D, Tweedie DJ, St George R, Chen LZ, and Li Y (2014) Generating an IVIVC for metabolism and liver enrichment of an HCV drug, faldaprevir, using a rat hepatocyte model (HepatoPac). Drug Metab Dispos 42:407-414.
24. Ring BJ, Chien JY, Adkison KK, Jones HM, Rowland M, Jones RD, Yates JW, Ku MS, Gibson CR, and He H, et al. (2011) PhRMA CPCDC initiative on predictive models of human pharmacokinetics, part 3: comparative assessment of prediction methods of human clearance. J Pharm Sci 100:4090-4110.
25. Sousa T, Paterson R, Moore V, Carlsson A, Abrahamsson B, and Basit AW (2008) The gastrointestinal microbiota as a site for the biotransformation of drugs. Int J Pharm 363:1-25.
26. Spahn-Langguth H and Benet LZ (1993) Microsomal acyl glucuronidation: enzyme-kinetic studies with labile glucuronides. Pharmacology 46:268-273.
27. Sulkowski MS, Asselah T, Lalezari J, Ferenci P, Fainboim H, Leggett B, Bessone F, Mauss S, Heo J, and Datsenko Y, et al. (2013a) Faldaprevir combined with pegylated interferon alfa-2a and ribavirin in treatment-naïve patients with chronic genotype 1 HCV: SILEN-C1 trial. Hepatology 57:2143-2154.
28. Sulkowski MS, Bourlière M, Bronowicki JP, Asselah T, Pawlotsky JM, Shafran SD, Pol S, Mauss S, Larrey D, and Datsenko Y, et al. (2013b) Faldaprevir combined with peginterferon alfa-2a and ribavirin in chronic hepatitis C virus genotype-1 patients with prior nonresponse: SILEN-C2 trial. Hepatology 57:2155-2163.
29. Swift B, Pfeifer ND, and Brouwer KL (2010) Sandwich-cultured hepatocytes: an in vitro model to evaluate hepatobiliary transporter-based drug interactions and hepatotoxicity. Drug Metab Rev 42:446-471.
30. Wang WW, Khetani SR, Krzyzewski S, Duignan DB, and Obach RS (2010) Assessment of a micropatterned hepatocyte coculture system to generate major human excretory and circulating drug metabolites. Drug Metab Dispos 38:1900-1905.
31. Webborn PJ, Parker AJ, Denton RL, and Riley RJ (2007) In vitro-in vivo extrapolation of hepatic clearance involving active uptake: theoretical and experimental aspects. Xenobiotica 37:1090-1109.
32. White PW, Llinàs-Brunet M, Amad M, Bethell RC, Bolger G, Cordingley MG, Duan J, Garneau M, Lagacé L, and Thibeault D, et al. (2010) Preclinical characterization of BI 201335, a C-terminal carboxylic acid inhibitor of the hepatitis C virus NS3-NS4A protease. Antimicrob Agents Chemother 54:4611-4618.
33. Yang J, Jamei M, Yeo KR, Rostami-Hodjegan A, and Tucker GT (2007) Misuse of the wellstirred model of hepatic drug clearance. Drug Metab Dispos 35:501-502.