This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jordan, R.
Right arrow Articles by Huggins, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jordan, R.
Right arrow Articles by Huggins, J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2009, p. 1817-1822, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01596-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

ST-246 Antiviral Efficacy in a Nonhuman Primate Monkeypox Model: Determination of the Minimal Effective Dose and Human Dose Justification {triangledown}

Robert Jordan,1 Arthur Goff,2 Annie Frimm,3 Michael L. Corrado,3 Lisa E. Hensley,2 Chelsea M. Byrd,1 Eric Mucker,2 Josh Shamblin,2 Tove' C. Bolken,1 Carly Wlazlowski,2 Wendy Johnson,2 Jennifer Chapman,2 Nancy Twenhafel,2 Shanthakumar Tyavanagimatt,1 Adams Amantana,1 Jarasvech Chinsangaram,1 Dennis E. Hruby,1* and John Huggins2

SIGA Technologies, Corvallis, Oregon,1 U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland,2 INC Research, Raleigh, North Carolina3

Received 2 December 2008/ Returned for modification 9 January 2009/ Accepted 2 February 2009

Therapeutics for the treatment of pathogenic orthopoxvirus infections are being sought. In the absence of patients with disease, animal models of orthopoxvirus disease are essential for evaluation of the efficacies of antiviral drugs and establishment of the appropriate dose and duration of human therapy. Infection of nonhuman primates (NHP) by the intravenous injection of monkeypox virus has been used to evaluate a promising therapeutic drug candidate, ST-246. ST-246 administered at 3 days postinfection (which corresponds to the secondary viremia stage of disease) at four different doses (from 100 mg/kg of body weight down to 3 mg/kg) once a day for 14 days was able to offer NHP 100% protection from a lethal infection with monkeypox virus and reduce the viral load and lesion formation. In NHP, the administration of ST-246 at a dose of 10 mg/kg/day for 14 days resulted in levels of blood exposure comparable to the levels attained in humans administered 400 mg in the fed state. These results suggest that administration of an oral dosage of 400 mg once daily for 14 days will be effective for the prevention or treatment of smallpox or monkeypox infections in humans.

* Corresponding author. Mailing address: SIGA Technologies, Inc., 4575 SW Research Way, Suite 230, Corvallis, OR 97333. Phone: (541) 753-2000. Fax: (541) 753-9999. E-mail: dhruby{at}siga.com

{triangledown} Published ahead of print on 17 February 2009.

Antimicrobial Agents and Chemotherapy, May 2009, p. 1817-1822, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01596-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Berhanu, A., King, D. S., Mosier, S., Jordan, R., Jones, K. F., Hruby, D. E., Grosenbach, D. W. (2009). ST-246 Inhibits In Vivo Poxvirus Dissemination, Virus Shedding, and Systemic Disease Manifestation. Antimicrob. Agents Chemother. 53: 4999-5009 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»