Pharmacology and Mechanisms of Action of Antiviral Drugs: Ribavirin Analogs

Advanced Therapy for Hepatitis C

Volumn , Issue , 2011, Pages 36-42

  Poordad, Fred ^a,b   Chee, Grace M ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b CEDARS SINAI MEDICAL CENTER   (United States)

Author keywords

Chronic hepatitis C; Hemolytic anemia; IMPDH; Levovirin; Merimepodib; Oral antivirals; Ribavirin; Ribavirin analog; Taribavirin

Indexed keywords

EID: 84885515161     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9781444346343.ch5     Document Type: Chapter

References (32)

1. Tam RC, Lau JYN, Hong J. Mechanisms of action of ribavirin in antiviral therapies. Antiviral Chem Chemother 2002;12: 261-72.
2. Tam RC, Pai B, Bard J, et al. Ribavirin polarized human T cell response towards a Type 1 cytokine profile. J Hepatol 1999;30: 376-82.
3. Hultgren C, Milich DR, Weiland W, Sallberg M. The antiviral compound ribavirin modulates the T helper (Th) 1/Th 2 subset balance in hepatitis B and C virus-specific immune responses. J Gen Virol 1998;79: 2381-91.
4. Abonyi ME, Lakatos PL. Ribavirin in the treatment of hepatitis C. Anticancer Res 2005;25: 1315-20.
5. Barnes E, Salio M, Cerundolo V, et al. Impact of alpha interferon and ribavirin on the function of maturing dendritic cells. Antimicrob Agents Chemother 2004;48: 3382-9.
6. Meier V, Burger, E, Mihm S, et al. Ribavirin inhibits DNA, RNA, and protein synthesis in PHA-stimulated human peripheral blood mononuclear cells: possible explanation for therapeutic efficacy in patients with chronic HCV infection. J Med Virol 2003;69: 50-58.
7. Brok J, Gluud LL, Gluud C. Ribavirin monotherapy for chronic hepatitis C infection: a Cochrane Hepato-Biliary Group systematic review and meta-analysis of randomized trials. Am J Gastroenterol 2006;101: 842-7.
8. Pawlotsky JM, Dahari H, Neumann AU, et al. Antiviral action of ribavirin in chronic hepatitis C. Gastroenterology 2004;126: 703-14.
9. Asahina Y, Izumi N, Enomoto N, et al. Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C. J Hepatol 2005;43: 623-9.
10. Hofmann WP, Polta A, Herrmann E, et al. Mutagenic effect of ribavirin on hepatitis C nonstructural 5B quasispecies in vitro and during antiviral therapy. Gastroenterology 2007;132: 921-30.
11. McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 1998;339(21): 1485-92.
12. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin comparedwith interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358: 958-65.
13. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347: 975-82.
14. McHutchison JG, Everson GT, Gordon SC, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009;360(18):1827-38.
15. Kwo P, Lawitz EJ, McCone J, et al. HCV SPRINT-1: Final results SVR 24 NS3 protease inhibitor boceprevir plus PegIFN alpha-2b/ribavirin HCV 1 treatment naï{dotless}ve patients. J Hepatol 2009;50(Suppl 1):S4.
16. Reddy KR, Shiffman ML, Morgan TR, et al. Impact of ribavirin dose reductions in hepatitis C virus genotype 1 patients completing peginterferon alfa-2a/ribavirin treatment. Clin Gastoenterol Hepatol 2007;5: 124-9.
17. McHutchison JG, Lawitz EJ, Shiffman ML, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 2009;361(6):580-93.
18. Hézode C, Forestier N, Dusheiko G, et al. Telaprevir and peginterferon with or without ribavirn for chronic HCV infection. N Engl J Med 2009;360(18):1839-50.
19. Lin C-C, Luu T, LourencoD, et al. Absorption, pharmacokinetics and excretion of levovirin in rats, dogs and cynomolgus monkeys. J Antimicrob Chemother 2003;51: 93-9.
20. Rossi S, Wright T, Lin C-C, et al. Phase I clinical studies of levovrin - a second generation ribavirin candidate. Hepatology 2001;34(4 Pt 2):327A.
21. Pockros P, Pessoa M, Diago M, et al. Combination of levovirin and pegylated interferon alfa-2a fails to generate an induction response comparable to ribavirin and pegylated interferon alfa-2a in patients with CHC. Antivir Ther 2004; 9:H17A32.
22. Hofmann WP, Polta A, Hermann E, et al. Mutagenic effect of ribavirin on hepatitis C nonstructural 5B quasispecies in vitro and during antiviral therapy. Gastroenterology 2007; 132: 921-30.
23. Huang y, Ostrowitzki S, Hill G, et al. Single-and multipledose pharmacokinetics of levorin valinate hydrochloride (R1518) in healthy volunteers. J Clin Pharmacol 2005;45: 578-88.
24. Wu JZ, Walker H, Lau JY, et al. Activation and deactivation of a broad-spectrum antiviral drug by a single enzyme: adenosine deaminase catalyzes two consecutive deamination reactions. Antimicrob Agents Chemother 2003;47(1):426-31.
25. Lin, C, Luu K, Lourenco D, Yeh L. Pharmacokinetics and metabolism of [14C]viramidine in rats and cynomolgus monkeys. Antimicrobial Agents Chemother 2003;47: 2458-63.
26. Lin C, Yeh L-T, Vitarella D, Hong Z. Taribavirin, a prodrug of ribavirin, shows better liver-targeting properties and safety profiles than ribavirin in animals. Anitviral ChemChemother 2003;14: 145-52.
27. Poordad F, Chee G. Taribavirin: a potential alternative to ribavirin. Future Virol 2009;4(2):113-20.
28. Lin CC, Philips L, Xu C, Yeh LT. Pharmacokinetics and safety of viramidine, a prodrug of ribavirin, in healthy volunteers. J Clin Pharmacol 2004;44(3):265-75.
29. Aora S, Xu, C, Teng A, et al. Ascending multiple-dose pharmacokinetics of viramidine, a prodrug of ribavirin, in adult subjectswith compensated hepatitis Cinfection. JClin Pharmacol 2005;45: 275-85.
30. Poordad F, Lawitz E, Shiffman ML, et al. Virologic response rates ofweight-based taribavirin versus ribavirin in treatment-naï{dotless}ve patients with genotype 1 chronic hepatitis C. Hepatology 2010;52(4):1208-15.
31. Markland W, McQuaid TJ, Jain J, et al. Broad-spectrum antiviral activity of the IMP dehydrogenase inhibitor VX-497: a comparison with ribavirin and demonstration of antiviral additivity with alpha interferon. Antimicrob Agents Chemother 2000;44(4):859-66.
32. Rustgi VK, Lee WM, Lawitz E, et al. Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders. Herpatology 2009; 50(6):1719-26.