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Amantadine-oseltamivir combination therapy for H5N1 influenza virus infection in mice.
Antivir Ther. 2007; 12(3):363-70.AT

Abstract

BACKGROUND

The clinical management of H5N1 influenza virus infection in humans remains unclear. Combination chemotherapy with drugs that target different viral proteins might be more effective than monotherapy.

METHODS

BALB/c mice were treated by oral gavage for 5 days with amantadine (1.5, 15 or 30 mg/kg/day) and oseltamivir (1 or 10 mg/kg/day) separately or in combination. Mice were challenged 24 h after initiation of treatment with 10 mouse 50% lethal doses of either amantadine-sensitive (having S31 in the M2 protein) or amantadine-resistant (having N31 in the M2 protein) recombinant A/Vietnam/1203/04 (H5N1) virus.

RESULTS

Combination treatment with amantadine (15 or 30 mg/kg/day) and oseltamivir (10 mg/kg/day) provided greater protection (60% and 90%, respectively) against lethal infection with amantadine-sensitive H5N1 virus than did monotherapy. Moreover, spread of the virus to the brain was prevented by both combination regimens. The efficacy of the drug combinations against amantadine-resistant H5N1 virus was comparable to that of oseltamivir alone. Oseltamivir produced a dose-dependent effect against both recombinant H5N1 viruses (P < 0.05) but did not provide complete protection against lethal infection. Importantly, no mutations in the HA, NA and M2 proteins were detected when the two drugs were used in combination.

CONCLUSIONS

Combination chemotherapy provided a survival advantage over single-agent treatment of mice inoculated with neurotropic H5N1 influenza virus. This strategy might be an option for the control of pandemic influenza viruses that are sensitive to amantadine. Combinations that include other drugs should be explored.

Authors+Show Affiliations

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17591026

Citation

Ilyushina, Natalia A., et al. "Amantadine-oseltamivir Combination Therapy for H5N1 Influenza Virus Infection in Mice." Antiviral Therapy, vol. 12, no. 3, 2007, pp. 363-70.
Ilyushina NA, Hoffmann E, Salomon R, et al. Amantadine-oseltamivir combination therapy for H5N1 influenza virus infection in mice. Antivir Ther (Lond). 2007;12(3):363-70.
Ilyushina, N. A., Hoffmann, E., Salomon, R., Webster, R. G., & Govorkova, E. A. (2007). Amantadine-oseltamivir combination therapy for H5N1 influenza virus infection in mice. Antiviral Therapy, 12(3), 363-70.
Ilyushina NA, et al. Amantadine-oseltamivir Combination Therapy for H5N1 Influenza Virus Infection in Mice. Antivir Ther (Lond). 2007;12(3):363-70. PubMed PMID: 17591026.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amantadine-oseltamivir combination therapy for H5N1 influenza virus infection in mice. AU - Ilyushina,Natalia A, AU - Hoffmann,Erich, AU - Salomon,Rachelle, AU - Webster,Robert G, AU - Govorkova,Elena A, PY - 2007/6/27/pubmed PY - 2007/8/7/medline PY - 2007/6/27/entrez SP - 363 EP - 70 JF - Antiviral therapy JO - Antivir. Ther. (Lond.) VL - 12 IS - 3 N2 - BACKGROUND: The clinical management of H5N1 influenza virus infection in humans remains unclear. Combination chemotherapy with drugs that target different viral proteins might be more effective than monotherapy. METHODS: BALB/c mice were treated by oral gavage for 5 days with amantadine (1.5, 15 or 30 mg/kg/day) and oseltamivir (1 or 10 mg/kg/day) separately or in combination. Mice were challenged 24 h after initiation of treatment with 10 mouse 50% lethal doses of either amantadine-sensitive (having S31 in the M2 protein) or amantadine-resistant (having N31 in the M2 protein) recombinant A/Vietnam/1203/04 (H5N1) virus. RESULTS: Combination treatment with amantadine (15 or 30 mg/kg/day) and oseltamivir (10 mg/kg/day) provided greater protection (60% and 90%, respectively) against lethal infection with amantadine-sensitive H5N1 virus than did monotherapy. Moreover, spread of the virus to the brain was prevented by both combination regimens. The efficacy of the drug combinations against amantadine-resistant H5N1 virus was comparable to that of oseltamivir alone. Oseltamivir produced a dose-dependent effect against both recombinant H5N1 viruses (P < 0.05) but did not provide complete protection against lethal infection. Importantly, no mutations in the HA, NA and M2 proteins were detected when the two drugs were used in combination. CONCLUSIONS: Combination chemotherapy provided a survival advantage over single-agent treatment of mice inoculated with neurotropic H5N1 influenza virus. This strategy might be an option for the control of pandemic influenza viruses that are sensitive to amantadine. Combinations that include other drugs should be explored. SN - 1359-6535 UR - https://www.unboundmedicine.com/medline/citation/17591026/Amantadine_oseltamivir_combination_therapy_for_H5N1_influenza_virus_infection_in_mice_ L2 - https://medlineplus.gov/birdflu.html DB - PRIME DP - Unbound Medicine ER -