Viramidine demonstrates better safety than ribavirin in monkeys but not rats

Drug and Chemical Toxicology

Volumn 27, Issue 3, 2004, Pages 191-211

  Dadgostari, Soheila ^a   Xu, Christine ^a   Yeh, Li Tain ^a   Lin, Chin Chung ^a   Vitarella, Domenico ^a  

^a Valeant Research and Development   (United States)

Author keywords

Erythroid hyperplasia of the bone marrow; Hemolytic anemia; Ribavirin; Safety; Viramidine

Indexed keywords

AMIDINE; HEMOGLOBIN; RIBAMIDINE; RIBAVIRIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BONE MARROW; CELL HYPERPLASIA; CONTROLLED STUDY; CONVALESCENCE; DRUG EFFECT; DRUG MEGADOSE; DRUG SAFETY; ERYTHROID CELL; FEMALE; HEMOGLOBIN DETERMINATION; HEMOLYTIC ANEMIA; MALE; MONKEY; NONHUMAN; PROTEIN BLOOD LEVEL; RAT; RETICULOCYTE COUNT;

ANIMALS; ANTIVIRAL AGENTS; AREA UNDER CURVE; BLOOD CELL COUNT; BODY TEMPERATURE; BODY WEIGHT; EATING; ELECTROCARDIOGRAPHY; EYE DISEASES; FEMALE; HEMODYNAMIC PROCESSES; MACACA FASCICULARIS; MALE; ORGAN SIZE; RATS; RATS, SPRAGUE-DAWLEY; RESPIRATORY MECHANICS; RIBAVIRIN;

ANIMALIA;

EID: 4544386821     PISSN: 01480545     EISSN: None     Source Type: Journal    
DOI: 10.1081/DCT-200031953     Document Type: Article

References (19)

1. Aldrich, M. B., Blackburn, M. R., Kellems, R. E. (2000). The importance of adenosine deaminase for lymphocyte development and function. Biochem. Biophys. Res. Commun. 272:311-315.
2. Apasov, S. G., Blackburn, M. R., Kellems, R. E., Smith, P. T., Sitkovsky, M. (2001). VAdenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling. J. Clin. Invest. 108(1):131-141.
3. Bloom, J. C., Brand, T. J. (2001). Toxic responses of the blood. In: Klassen, C. D., ed. Cassarett and Doull's Toxicology, The Basic Science of Poisons. 6th ed. New York: McGraw Hill, Medical Publishing Division, pp. 389-419.
4. Canonico, P. G., Kastello, M. D., Cosgriff, T. M., Donovan, J. C., Ross, P. E., Spears, C. T., Stephen, E. L. (1984). Hematological and bone marrow effects of ribavirin in rhesus monkeys. Toxicol. Appl. Pharmacol. 74:163-172.
5. Connor, E., Morrison, S., Lane, J., Oleske, J., Sonke, R. L., Connor, J. (1993). Safety and tolerance and pharmacokinetics of systemic ribavirin in children with human immunodificiency virus infections. Antimicrob. Agents Chemother. 37:532-539.
6. Dean, J. H., Murray, M. J. (1991). Toxic responses of the immune system. In: Amudur, M. O., Doull, J., Klassen, C. D., eds. Cassarett and Doull's Toxicology, The Basic Science of Poisons. New York: McGraw Hill, Medical Publishing Division, pp. 282-333.
7. Di Bisceglie, A. M., McHutchison, J., Rice, C. M. (2002). New therapeutic strategies for hepatitis C. Hepatology 35(1):224-231.
8. Fried, M. W. (2002). Side effects of therapy of hepatitis C and their management. Hepatology 36(5 Suppl 1):S237-244.
9. Hillyard, I. W. (1980). The preclinical toxicology and safety of ribavirin. In: Smith, R. A., Kirkpatrick, W., eds. RIBAVIRIN, A Broad Spectrum Antiviral Agent. New York: Academic Press, pp. 59-72.
10. Hltgren, C., Milich, D. R., Weiland, O., Sallberg, M. (1998). The antiviral compound ribavirin modulates the T helper (Th) 1/Th2 subset balance in hepatitis B and C virus-specific immune responses. J. Gen. Virol. 79:2381-2391.
11. Lertora, J. J., Rege, A. B., Lacour, J. T., Ferencz, N., George, W. J., VanDyke, R. B., Agrawal, K. C., Hyslop, N. E. (1991). Pharmacokinetics and long-term tolerance to ribavirin in asymptomatic patients infected with human immunodeficiency virus. Clin. Pharmacol. Therap. 50:442-449.
12. Lin, C. C., Yeh, L. T., Vitarella, D., Hong, Z. (2003a). Viramidine, a prodrug of ribavirin, shows better liver-targeting property and safety profiles in animals. Antivir. Chem. Chemother. 14:145-152.
13. 14C] ribavirin in rats and cynomolgus monkeys. Antimicrob. Agents Chemother. 47:1395-1398.
14. NTP Report Number IMM90010. The Immunotoxicity of Ribavirin (CAS No. 36791-04-5) in Female C57B1/6 Mice. National Toxicology Program (NTP), Organ System Toxicity Abstracts (Immunology Studies), August 1989.
15. Page, T., Conner, J. D. (1990). The metabolism of ribavirin in erythrocytes and nucleated cell. Int. J. Biochem. 22:379-383.
16. Pol, S., Nalpas, B., Bourliere, M., Couzigou, P., Tran, A., Abergel, A., Zarski, J. P., Berthelot, P., Brechot, C. (2003). Combination of ribavirin and interferon-alfa surpasses high doses of interferon-alfa alone in patients with genotype 1b-related chronic hepatitis C. Hepatology 31:1338-1344.
17. Tam, R. C., Ramasamy, K., Bard, J., Pai, B., Lim, C., Averett, D. R. (2000). The ribavirin ananlouge ICN 17261 demonstrates reduced toxicity and antiviral effects with retention of both immunomodulatory activity and reduction of hepatitis-induced serum alanine aminotransferase levels. Antimicrob. Agents Chemother. 44(5):1276-1283.
18. Tam, R. C., Lau, J. Y., Hong, Z. (2001). Mechanisms of action of ribavirin in antiviral therapies. Antivir. Chem. Chemother. 12(5):261-272.
19. Wu, J. Z., Walker, H., Lau, J. Y. N., Hong, Z. (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(1):426-431.