Preclinical Pharmacokinetics and in Vitro Metabolism of Asunaprevir (BMS-650032), a Potent Hepatitis C Virus NS3 Protease Inhibitor

Journal of Pharmaceutical Sciences

Volumn 104, Issue 9, 2015, Pages 2813-2823

  Mosure, Kathleen W ^a   Knipe, Jay O ^a   Browning, Marc ^a   Arora, Vinod ^a   Shu, Yue Zhong ^a   Phillip, Thomas ^a   McPhee, Fiona ^a   Scola, Paul ^a   Balakrishnan, Anand ^a   Soars, Matthew G ^a   Santone, Kenneth ^a   Sinz, Michael ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

ADME; antiinfectives; bioavailability; clearance; disposition; hepatic clearance; in vitro in vivo correlations (IVIVC); metabolism; P glycoprotein; pharmacokinetics

Indexed keywords

ASUNAPREVIR; CYTOCHROME P450 1A2; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; NONSTRUCTURAL PROTEIN 3; ANTIVIRUS AGENT; CYTOCHROME P450 3A; CYTOCHROME P450 INHIBITOR; ISOQUINOLINE DERIVATIVE; MULTIDRUG RESISTANCE PROTEIN; NS3 PROTEIN, HEPATITIS C VIRUS; PROTEINASE INHIBITOR; SULFONAMIDE; VIRUS PROTEIN;

AEROBIC METABOLISM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG METABOLISM; ELIMINATION HALF-LIFE; ENZYME INHIBITION; FEMALE; HEPATITIS C VIRUS; HUMAN; HUMAN CELL; HYDROXYLATION; IN VITRO STUDY; IN VIVO STUDY; INTESTINE ABSORPTION; INTRINSIC CLEARANCE; LIVER CELL; LIVER MICROSOME; MALE; MAXIMUM PLASMA CONCENTRATION; MEAN RESIDENCE TIME; METABOLIC STABILITY; MOUSE; NONHUMAN; PHENOTYPE; PLASMA CLEARANCE; RAT; REPLICON; TIME TO MAXIMUM PLASMA CONCENTRATION; VIRUS LOAD; VOLUME OF DISTRIBUTION AT STEADY-STATE; ANIMAL; ANTAGONISTS AND INHIBITORS; BILE; BIOAVAILABILITY; DOG; DRUG EFFECTS; ENZYMOLOGY; HEPACIVIRUS; LIVER; MACACA FASCICULARIS; METABOLISM; OXIDATION REDUCTION REACTION; SPRAGUE DAWLEY RAT;

ANIMALS; ANTIVIRAL AGENTS; BILE; BIOLOGICAL AVAILABILITY; CYTOCHROME P-450 CYP3A; CYTOCHROME P-450 ENZYME INHIBITORS; DOGS; HEPACIVIRUS; HEPATOCYTES; HUMANS; ISOQUINOLINES; LIVER; MACACA FASCICULARIS; MALE; MICE; MICROSOMES, LIVER; OXIDATION-REDUCTION; P-GLYCOPROTEIN; PROTEASE INHIBITORS; RATS; RATS, SPRAGUE-DAWLEY; SULFONAMIDES; VIRAL NONSTRUCTURAL PROTEINS;

EID: 84939271207     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.24356     Document Type: Article

References (37)

1. Shepard CW, Finelli L, Alter MJ,. 2005. Global epidemiology of hepatitis C virus infection. The Lancet Infect Dis 5 (9): 558-567.
2. Lauer GM, Walker BD,. 2001. Hepatitis C virus infection. N Engl J Med 345 (1): 41-52.
3. Ghany MG, Strader DB, Thomas DL, Seeff LB,. 2009. Diagnosis, management, and treatment of hepatitis C: an update. Hepatol 49 (4): 1335-1374.
4. Sarbah SA, Younossi ZM,. 2000. Hepatitis C: an update on the silent epidemic. J Clin Gastroenterol 30 (2): 125-143.
5. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, Muir AJ, Ferenci P, Flisiak R, George J, Rizzetto M, Shouval D, Sola R, Terg RA, Yoshida EM, Adda N, Bengtsson L, Sankoh AJ, Kieffer TL, George S, Kauffman RS, Zeuzem S,. 2011. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 364 (25): 2405-2416.
6. Poordad F, McCone J Jr., Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP,. 2011. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 364 (13): 1195-1206.
7. McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, McNair L, Alam J, Muir AJ,. 2009. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 360 (18): 1827-1838.
8. Fried MW, Buti M, Dore GJ, Flisiak R, Ferenci P, Jacobson I, Marcellin P, Manns M, Nikitin I, Poordad F, Sherman M, Zeuzem S, Scott J, Gilles L, Lenz O, Peeters M, Sekar V, De Smedt G, Beumont-Mauviel M,. 2013. Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naive genotype 1 hepatitis C: the randomized PILLAR study. Hepatol 58 (6): 1918-1929.
9. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL, Jr., Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J,. 2002. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347 (13): 975-982.
10. McPhee F, Sheaffer AK, Friborg J, Hernandez D, Falk P, Zhai G, Levine S, Chaniewski S, Yu F, Barry D, Chen C, Lee MS, Mosure K, Sun LQ, Sinz M, Meanwell NA, Colonno RJ, Knipe J, Scola P,. 2012. Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir (BMS-650032). Antimicrob Agents Chemother 56 (10): 5387-5396.
11. Everson GT, Sims KD, Rodriguez-Torres M, Hezode C, Lawitz E, Bourliere M, Loustaud-Ratti V, Rustgi V, Schwartz H, Tatum H, Marcellin P, Pol S, Thuluvath PJ, Eley T, Wang X, Huang SP, McPhee F, Wind-Rotolo M, Chung E, Pasquinelli C, Grasela DM, Gardiner DF,. 2014. Efficacy of an interferon- and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1 infection. Gastroenterol 146 (2): 420-429.
12. Kumada H, Suzuki Y, Ikeda K, Toyota J, Karino Y, Chayama K, Kawakami Y, Ido A, Yamamoto K, Takaguchi K, Izumi N, Koike K, Takehara T, Kawada N, Sata M, Miyagoshi H, Eley T, McPhee F, Damokosh A, Ishikawa H, Hughes E,. 2014. Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. Hepatology 59 (6): 2083-2091.
13. Manns M, Pol S, Jacobson IM, Marcellin P, Gordon SC, Peng CY, Chang TT, Everson GT, Heo J, Gerken G, Yoffe B, Towner WJ, Bourliere M, Metivier S, Chu CJ, Sievert W, Bronowicki JP, Thabut D, Lee YJ, Kao JH, McPhee F, Kopit J, Mendez P, Linaberry M, Hughes E, Noviello S, on behalf of the H-DST. 2014. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet 384: 1597-1605.
14. Company B-MS. 2014. Japan Approves First All-Oral, Interferon- and Ribavirin-Free Hepatitis C Treatment, Daklinza® (daclatasvir) and Sunvepra® (asunaprevir) Dual Regimen Jult 7, 2014 ed.
15. Scola PM, Sun LQ, Wang AX, Chen J, Sin N, Venables BL, Sit SY, Chen Y, Cocuzza A, Bilder DM, D'Andrea SV, Zheng B, Hewawasam P, Tu Y, Friborg J, Falk P, Hernandez D, Levine S, Chen C, Yu F, Sheaffer AK, Zhai G, Barry D, Knipe JO, Han YH, Schartman R, Donoso M, Mosure K, Sinz MW, Zvyaga T, Good AC, Rajamani R, Kish K, Tredup J, Klei HE, Gao Q, Mueller L, Colonno RJ, Grasela DM, Adams SP, Loy J, Levesque PC, Sun H, Shi H, Sun L, Warner W, Li D, Zhu J, Meanwell NA, McPhee F,. 2014. The Discovery of Asunaprevir (BMS-650032), An Orally Efficacious NS3 Protease Inhibitor for the Treatment of Hepatitis C Virus Infection. J Med Chem 57 (5): 1730-1752.
16. Crespi CL, Miller VP, Penman BW,. 1997. Microtiter plate assays for inhibition of human, drug-metabolizing cytochromes P450. Anal Biochem 248 (1): 188-190.
17. Browning MR, Drexler DM, Olah TV, Morgan DG,. 2010. Simultaneous bioanalysis of a phosphate prodrug and its parent compound using a multiplexed LC-MS method. Bioanalysis 2 (4): 745-753.
18. Houston JB,. 1994. Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance. Biochem Pharmacol 47 (9): 1469-1479.
19. Iwatsubo T, Hirota N, Ooie T, Suzuki H, Shimada N, Chiba K, Ishizaki T, Green CE, Tyson CA, Sugiyama Y,. 1997. Prediction of in vivo drug metabolism in the human liver from in vitro metabolism data. Pharmacol Ther 73 (2): 147-171.
20. Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, MacIntyre F, Rance DJ, Wastall P,. 1997. The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. J Pharmacol Exp Ther 283 (1): 46-58.
21. Davies B, Morris T,. 1993. Physiological parameters in laboratory animals and humans. Pharm Res 10 (7): 1093-1095.
22. Chayama K, Takahashi S, Toyota J, Karino Y, Ikeda K, Ishikawa H, Watanabe H, McPhee F, Hughes E, Kumada H,. 2012. Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders. Hepatol 55 (3): 742-748.
23. Suzuki Y, Ikeda K, Suzuki F, Toyota J, Karino Y, Chayama K, Kawakami Y, Ishikawa H, Watanabe H, Hu W, Eley T, McPhee F, Hughes E, Kumada H,. 2013. Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options. J Hepatol 58 (4): 655-662.
24. Hassanein T, Sims KD, Bennett M, Gitlin N, Lawitz E, Nguyen T, Webster L, Younossi ZM, Schwartz H, Thuluvath PJ, Zhou H, Rege B, McPhee F, Zhou N, Wind-Rotolo M, Chung E, Griffies A, Grasela D, Gardiner DF,. 2014. All-Oral Therapy With Daclatasvir In Combination With Asunaprevir And Bms-791325 For Treatment-Naive Patients With Chronic HCV Genotype 4 Infection. J Hepatol 60 (1): S472.
25. Eley T, He B, Huang SP, Stonier M, Bedford B, Kandoussi H, Gardiner D, Sims K, Wenying L, Bertz R,. 2013. The effect of multiple-dose Ketoconazole and the effect of multiple-dose Rifampin on the pharmacokinetics (PK) of the HCV NS3 Protease Inhibitor Asunaprevir. ed., 8th International Workshop on Clinical Pharmacology of Hepatitis Therapy-Boston MA.
26. Eley T, Sevinsky H, Huang SP, He B, Zhu K, Kandoussi H, Gardiner D, Grasela DM, Bertz R, Bifano M,. 2014. The pharmacokinetics of daclatasvir and asunaprevir administered in combination in studies in healthy subjects and patients infected with hepatitis C virus. Clin Drug Investig 34 (9): 661-671.
27. Soars MG, Grime K, Sproston JL, Webborn PJ, Riley RJ,. 2007. Use of hepatocytes to assess the contribution of hepatic uptake to clearance in vivo. Drug Metab Dispos 35 (6): 859-865.
28. Mahmood I, Yuan R,. 1999. A comparative study of allometric scaling with plasma concentrations predicted by species-invariant time methods. Biopharm Drug Dispos 20 (3): 137-144.
29. Eley T, He B, Huang S-P, Li W, Pasquinelli C, Rodrigues AD, Grasela DM, Bertz R,. 2013. Pharmacokinetics of the NS3 Protease Inhibitor, Asunaprevir (ASV, BMS-650032), in Phase I Studies in Subjects With or Without Chronic Hepatitis C. Clinical Pharmacol Drug Dev 2 (4): 316-327.
30. Gardiner P, Paine SW,. 2011. The impact of hepatic uptake on the pharmacokinetics of organic anions. Drug Metab Dispos 39 (10): 1930-1938.
31. Paine SW, Menochet K, Denton R, McGinnity DF, Riley RJ,. 2011. Prediction of human renal clearance from preclinical species for a diverse set of drugs that exhibit both active secretion and net reabsorption. Drug Metab Dispos 39 (6): 1008-1013.
32. Koike K, Moriya K, Matsuura Y,. 2010. Animal models for hepatitis C and related liver disease. Hepatol Res 40 (1): 69-82.
33. Jenkins S, Scola P, McPhee F, Knipe J, Gesenberg C, Sinz M, Arora V, Pilcher G, Santone K,. 2014. Preclinical Pharmacokinetics and In Vitro Metabolism of BMS-605339: A Novel HCV NS3 Protease Inhibitor. J Pharm Sci 103 (6): 1891-1902.
34. Seiwert SD, Andrews SW, Jiang Y, Serebryany V, Tan H, Kossen K, Rajagopalan PT, Misialek S, Stevens SK, Stoycheva A, Hong J, Lim SR, Qin X, Rieger R, Condroski KR, Zhang H, Do MG, Lemieux C, Hingorani GP, Hartley DP, Josey JA, Pan L, Beigelman L, Blatt LM,. 2008. Preclinical characteristics of the hepatitis C virus NS3/4A protease inhibitor ITMN-191 (R7227). Antimicrob Agents Chemother 52 (12): 4432-4441.
35. Cheng K-C, Li C, Liu T, Wang G, Hsieh Y, Pavlosky A, Broske L, Prelusky D, Liu R, White RE, Uss AE, Gupta S, Njoroge FC,. 2009. Use of pre-clinical in vitro and in vivo pharmacokinetics for the selection of a potent hepatitis C virus protease inhibitor, Boceprevir, for clinical development. Lett drug des and discov 6 (4): 312-318.
36. Scola PM, Wang AX, Good AC, Sun LQ, Combrink KD, Campbell JA, Chen J, Tu Y, Sin N, Venables BL, Sit SY, Chen Y, Cocuzza A, Bilder DM, D'Andrea S, Zheng B, Hewawasam P, Ding M, Thuring J, Li J, Hernandez D, Yu F, Falk P, Zhai G, Sheaffer AK, Chen C, Lee MS, Barry D, Knipe JO, Li W, Han YH, Jenkins S, Gesenberg C, Gao Q, Sinz MW, Santone KS, Zvyaga T, Rajamani R, Klei HE, Colonno RJ, Grasela DM, Hughes E, Chien C, Adams S, Levesque PC, Li D, Zhu J, Meanwell NA, McPhee F,. 2014. Discovery and Early Clinical Evaluation of BMS-605339, a Potent and Orally Efficacious Tripeptidic Acylsulfonamide NS3 Protease Inhibitor for the Treatment of Hepatitis C Virus Infection. J Med Chem 57 (5): 1708-1729.
37. Wajima T, Yano Y, Fukumura K, Oguma T,. 2004. Prediction of human pharmacokinetic profile in animal scale up based on normalizing time course profiles. J Pharm Sci 93 (7): 1890-1900.