Giuseppe
Emeritus
[Source: Antimicrobial Agents and Chemotherapy, full text: (LINK). Abstract, edited.]
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Pharmacokinetic and Pharmacodynamic Modeling to Determine the Human Dose of ST-246? to Protect Against Smallpox
Janet M. Leeds 1, Frederique Fenneteau 2, Nathalie H. Gosselin 2, Mohamad Samer Mouksassi 2, Nastya Kassir 2, JF Marier 2, Yali Chen 1, Doug Grosenbach 1, Annie E. Frimm 1, Kady M. Honeychurch 1, Jarasvech Chinsangaram 1, Shanthakumar R. Tyavanagimatt 1, Dennis E. Hruby 1,# and Robert Jordan 1
Author Affiliations: <SUP>1</SUP>SIGA Technologies, 4575 SW Research Way, Suite 230, Corvallis, OR 97333, U.S.A.; <SUP>2</SUP>Pharsight Consulting Services, a Division of Certara, 2000 Peel St., Suite 570, Montr?al, Qu?bec, Canada H3A 2W5
ABSTRACT
Although smallpox has been eradicated, the United States government considers it a ?Material Threat? and has funded the discovery and development of potential therapeutic compounds. As reported here, the human efficacious dose for one of these compounds, ST-246, was determined using efficacy studies in non-human primates (NHPs) together with pharmacokinetic and pharmacodynamic analysis that predicted the appropriate dose and exposure levels to provide therapeutic benefit in humans. The efficacy analysis combined the data from studies conducted at three separate facilities that evaluated treatment following infection of a closely related virus, monkeypox virus (MPXV), in a total of 96 NHPs. The effect of infection on ST-246 pharmacokinetics in NHPs was applied to humans using population pharmacokinetic models. Exposure at the selected human dose of 600 mg is more than four-fold higher than the lowest efficacious dose in NHPs and is predicted to provide protection to more than 95% of the population.
FOOTNOTES
# Corresponding Author: SIGA Technologies, 4575 SW Research Way, Suite 230, Corvallis, OR 97333, U.S.A., E-mail: dhruby@siga.com
Copyright ? 2012, American Society for Microbiology. All Rights Reserved.
-Janet M. Leeds 1, Frederique Fenneteau 2, Nathalie H. Gosselin 2, Mohamad Samer Mouksassi 2, Nastya Kassir 2, JF Marier 2, Yali Chen 1, Doug Grosenbach 1, Annie E. Frimm 1, Kady M. Honeychurch 1, Jarasvech Chinsangaram 1, Shanthakumar R. Tyavanagimatt 1, Dennis E. Hruby 1,# and Robert Jordan 1
Author Affiliations: <SUP>1</SUP>SIGA Technologies, 4575 SW Research Way, Suite 230, Corvallis, OR 97333, U.S.A.; <SUP>2</SUP>Pharsight Consulting Services, a Division of Certara, 2000 Peel St., Suite 570, Montr?al, Qu?bec, Canada H3A 2W5
ABSTRACT
Although smallpox has been eradicated, the United States government considers it a ?Material Threat? and has funded the discovery and development of potential therapeutic compounds. As reported here, the human efficacious dose for one of these compounds, ST-246, was determined using efficacy studies in non-human primates (NHPs) together with pharmacokinetic and pharmacodynamic analysis that predicted the appropriate dose and exposure levels to provide therapeutic benefit in humans. The efficacy analysis combined the data from studies conducted at three separate facilities that evaluated treatment following infection of a closely related virus, monkeypox virus (MPXV), in a total of 96 NHPs. The effect of infection on ST-246 pharmacokinetics in NHPs was applied to humans using population pharmacokinetic models. Exposure at the selected human dose of 600 mg is more than four-fold higher than the lowest efficacious dose in NHPs and is predicted to provide protection to more than 95% of the population.
FOOTNOTES
# Corresponding Author: SIGA Technologies, 4575 SW Research Way, Suite 230, Corvallis, OR 97333, U.S.A., E-mail: dhruby@siga.com
Copyright ? 2012, American Society for Microbiology. All Rights Reserved.
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