Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2487416 | Journal of Pharmaceutical Sciences | 2008 | 10 Pages |
Abstract
The pharmacokinetics of DSâ96, an Nâalkylhomospermine analog designed to sequester bacterial lipopolysaccharides, has been determined in rodent species. The elimination halfâlife in mice and rats are about 400 and 500 min, respectively, with other PK parameters being quite similar in the two rodent species. Interestingly, the mouse intravenous plasma concentration time curves exhibit an apparent absorption phase. While the rat intravenous data did not exhibit a pronounced apparent absorption phase immediately following injection, plasma levels did increase between 10 and 30 min following an expected drop from time 0 to 5 min. The data are consistent with firstâpass uptake, possibly by the lung, with back diffusion as a function of time. The observed Cmax values of 1.36 µg/mL in the mouse intraperitoneal model suggest that a plasma concentration of 0.5-1 µg/mL corresponds to complete protection for a 200 ng/animal dose of intraperitoneally administered LPS in the Dâgalactosamineâprimed model of endotoxinâinduced lethality. © 2008 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 97:5376-5385, 2008
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Authors
Anurupa Shrestha, Rongti Li, Diptesh Sil, Neha N. Pardeshi, Nancy Schwarting, Karl S. Schorno, Roger A. Rajewski, Apurba Datta, Sunil A. David,