Toll-like receptor 4 (TLR4) antagonist. Synthetic analog of the lipid A component of endotoxin, a major constituent of the outer membrane of Gram negative bacteria. Prepn: W. J. Christ et al., WO 9639411; eidem, US 5750664 (1996, 1998 both to Eisai). Pharmacology: M. Mullarkey et al., J. Pharmacol. Exp. Ther. 304, 1093 (2003). Clinical pharmacokinetics: Y. N. Wong et al., J. Clin. Pharmacol. 43, 735 (2003); and lipid distribution profile: D. P. Rossignol et al., Antimicrob. Agents Chemother. 48, 3233 (2004). Clinical evaluation in experimental endotoxemia: M. Lynn et al., J. Pharmacol. Exp. Ther. 308, 175 (2004). Review of pharmacology and clinical experience: D. P. Rossignol, M. Lynn, Curr. Opin. Investig. Drugs 6, 496-502 (2005).
In treatment of severe sepsis.
Antisepsis