Safety and Pharmacokinetics of ST-246 in Mice, Rabbits, and Monkeys
Author Information
Author(s): Chen Yali, Amantana Adams, Tyavanagimatt Shanthakumar R., Zima Daniela, Yan X. Steven, Kasi Gopi, Weeks Morgan, Stone Melialani A., Weimers William C., Samuel Peter, Tan Ying, Jones Kevin F., Lee Daniel R., Kickner Shirley S., Saville Bradley M., Lauzon Martin, McIntyre Alan, Honeychurch Kady M., Jordan Robert, Hruby Dennis E., Leeds Janet M.
Primary Institution: SIGA Technologies, Corvallis, Oregon, United States of America
Hypothesis
The pharmacokinetics of ST-246 after IV infusions in mice, rabbits, and nonhuman primates were compared to those obtained after oral administration.
Conclusion
Longer IV infusions of ST-246 are necessary to mimic plasma exposure observed after oral administration and to avoid toxicity associated with high peak plasma concentrations.
Supporting Evidence
- ST-246 is an antiviral drug in clinical development for treating orthopoxvirus infections.
- The study found that shorter IV infusions at higher doses resulted in decreased clearance.
- Dose-limiting central nervous system effects were identified in all three species.
- The administration of ST-246 was well tolerated as a slow IV infusion.
Takeaway
This study looked at how a new medicine called ST-246 works in different animals when given through a vein or by mouth, finding that giving it slowly through a vein is safer.
Methodology
The study compared pharmacokinetics and tolerability of ST-246 administered via IV infusion and oral administration in mice, rabbits, and nonhuman primates.
Limitations
The study was conducted in animal models, which may not fully predict human responses.
Participant Demographics
Mice, rabbits, and nonhuman primates were used in the study.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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