Disposition and Metabolic Profiles of [14C]Viramidine and [ 14C]Ribavirin in Rat and Monkey Red Blood Cells and Liver

Antimicrobial Agents and Chemotherapy

Volumn 48, Issue 5, 2004, Pages 1872-1875

  Lin, Chin Chung ^a,b   Lourenco, David ^a   Xu, Guifen ^a   Yeh, Li Tain ^a  

^a Valeant Research and Development   (United States)

^b Valeant Pharmaceuticals International   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RIBAMIDINE; RIBAVIRIN; RIBAVIRIN DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG ABSORPTION; DRUG DISPOSITION; DRUG LIVER LEVEL; DRUG METABOLISM; DRUG STRUCTURE; ERYTHROCYTE; MALE; NONHUMAN; PRIORITY JOURNAL; RADIOACTIVITY; RAT;

ANIMALS; ANTIVIRAL AGENTS; AREA UNDER CURVE; BIOTRANSFORMATION; CHROMATOGRAPHY, DEAE-CELLULOSE; ERYTHROCYTES; LIVER; MACACA FASCICULARIS; MALE; RATS; RATS, SPRAGUE-DAWLEY; RIBAVIRIN;

EID: 2142659317     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.48.5.1872-1875.2004     Document Type: Article

References (22)

1. Canonico, P. G., M. D. Kastello, C. T. Spears, J. R. Brown, E. A. Jacjsib, and D. E. Jenkins. 1984. Effect of ribavirin on red blood cells. Toxicol. Appl. Pharmacol. 74:155-162.
2. 14C-ribavirin: distribution and pharmacokinetic studies in rats, baboon and man, p. 83-98. In R. A. Smith and W. Yirkpatrick (ed.), Ribavirin: a broad spectrum antiviral agent. Academic Press, Inc., New York, N.Y.
3. Ferrara, E. A., J. S. Oishi, R. W. Wannemacher, and E. L. Stephen. 1981. Plasma disappearance, urine excretion, and tissue distribution of ribavirin in rats and rhesus monkeys. Antimicrob. Agents Chemother. 19:1042-1049.
4. Fried, M. W., M. L. Shiffman, K. R. Reddy, C. Smith, G. Marinos, F. L. Goncales, D. Haussinger, M. Diago, G. Carosi, D. Dhumeaux, A. Craxi, A. Lin, J. Hoffman, and J. Yu. 2002. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N. Engl. J. Med. 347:975-982.
5. Jarvis, S. M., J. A. Thorn, and P. Glue. 1998. Ribavirin uptake by human erythrocytes and the involvement of nitrobenzylthioinosine-sensitive (es)-nucleoside transporters. Br. J. Pharmacol. 123:1587-1592.
6. Laskin, O. L, J. A. Longstreth, C. A. Hart, D. Scavuzzo, C. M. Kalman, J. D. Connor, and R. B. Roberts. 1987. Ribavirin disposition in high-risk patients for acquired immunodeficiency syndrome. Clin. Pharmacol. Ther. 47:546-555.
7. Leotora, J. J., A. B. Rege, J. T. Lacour, N. Frenez, W. J. George, R. B. Vandyke, K. C. Agarwal, and N. E. Hyslop. 1991. Pharmacokinetics and long-term tolerance to ribavirin in asymptomatic patients infected with human immunodeficiency virus. Clin. Pharmacol. Ther. 50:442-449.
8. 14C]viramidine in rats and cynomolgus monkeys. Antimicrob. Agents Chemother. 47:2458-2463.
9. 14C]ribavirin in rats and cynomolgus monkeys. Antimicrob. Agents Chemother. 47:1395-1398.
10. Lin, C., L. Yeh, D. Vitarella, and Z. Hong. 2003. Viramidine, a prodrug of ribavirin, shows a better liver-targeting property and a better safety profile than ribavirin in animals. Antiviral Chem. Chemother. 14:145-152.
11. Lindsay, K. L., C. Trepo, T. Heintges, M. L. Shiffman, S. C. Gordon, J. C. Hoefs, E. R. Sehiff, Z. D. Goodman, M. Laughlin, R. Yao, and J. K. Albrecht. 2001. A randomized double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology 34:395-403.
12. Mann, M. P., J. G. McHutchison, S. C. Gordon, V. K. Rustgi, M. Shiffman, R. Reindollar, Z. D. Goodman, K. Koury, M. Ling, J. K. Albrecht, and The Internatl. Hepatitis Interventional Therapy Group. 2001. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C; a randomized trial. Lancet 358:958-965.
13. McHutchison, J. G., S. C. Gordon, E. R. Schiff, M. D. Mitchell, M. L. Shiffmann, W.-M. Lee, V. K. Rustgi, Z. D. Goodman, M. H. Ling, S. Cort, and J. K. Albrecht. 1998. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N. Engl. J. Med. 339:1485-1492.
14. Miller, J. P., L. J. Kigwana, D. G. Streeter, R. K. Robins, L. N. Simon, and J. Roboz. 1977. The relationship between the metabolism of ribavirin and its proposed mechanism of action. Ann. N. Y. Acad. Sci. 248:211-229.
15. Page, T., and J. D. Conners. 1990. The metabolism of ribavirin in erythro-cytes and nucleated cells. Int. J. Biochem. 22:379-383.
16. Poynard, T., P. Marcellin, S. S. Lee, C. Nieerau, G. Minuk, G. Ideo, and V. H. Bain, J. Heathcote, S. Zeuzem, C. Trepo, and J. Albrecht. 1998. Randomized trial of interferon alfa-2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alfa-2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet 352:1426-1432.
17. Sidwell, R. W., J. H. Huffman, G. P. Khare, L. B. Allen, J. T. Witkowski, and R. K. Robins. 1972. Broad-spectrum antiviral activity of virazole: 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. Science 177:705-706.
18. Smee, D. F., and T. R. Matthews. 1986. Metabolism of ribavirin in respiratory syncytial virus-infected and uninfected cells. Antimicrob. Agents Chemother. 30:117-121.
19. Stephen, E. L., D. E. Jones, C. J. Peters, G. A. Eddy, P. S. Loizeaux, and P. B. Jahrling. 1980. Ribavirin treatment of toga-, arena-, and bunyavirus infections in subhuman primates and other laboratory animal species, p. 169-183. In R. A. Smith and W. Kirkpatrick (ed.), Ribavirin: a broad spectrum antiviral agent. Academic Press, Inc., New York, N.Y.
20. Wills, R. C., D. A. Carson, and J. E. Seegmiller. 1978. Adenosine kinase initiates the major route of ribavirin activation in a cultured human cell line. Proc. Natl. Sci. USA 75:3042-3044.
21. Wu, J. Z., H. Walker, J. Y. Lau, and Z. Hong. 2003. Activation and deactivation of a broad-spectrum antiviral drug by a single enzyme: adenosine deaminase catalyzes two consecutive deamination reactions. Antimicrob. Agents Chemother. 47:426-431.
22. Zimmerman. T. P., and R. D. Deeprose. 1978. Metabolism of 5-amino-β-D-ribofuranosylimidazole-4-carboxamide and related five-membered hetrocycles to 5′-triphosphates in human blood and L517 Y cells. Biochem. Pharmacol. 27:709-716.