We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Safety, pharmacokinetics and pharmacodynamics of four-hour intravenous infusions of eritoran in healthy Japanese and Caucasian men.
- Authors
Aikawa, Naoki; Okubo, Yoshio; Lynn, Melvyn; Rossignol, Daniel P; Wong, Y Nancy; Schuck, Edgar; Kitahara, Yasumi; Nakano, Tomohisa; Sivak, Olena; Wasan, Kishor M; Nagy, Christa; Yen, Mark
- Abstract
Eritoran, a synthetic analogue of lipid A, has been shown to bind to TLR4/MD-2 complex and thereby block the interaction of endotoxins with TLR4. We report here the results of a study conducted to assess the single-dose safety and tolerability, as well as the pharmacokinetics and pharmacodynamics, of eritoran infusion in Japanese and Caucasian healthy adult men. Sixty-four men (aged 20–45 years; body mass index 18–30 kg/m2) were randomized into four groups: 4-mg total dose (six Japanese and six Caucasian men); 12-mg total dose (12 Japanese and 12 Caucasian men); 28-mg total dose (six Japanese and six Caucasian men); and placebo (eight Japanese and eight Caucasian men). Eritoran in single doses up to 28 mg over 4 h was well tolerated, with no apparent ethnic differences noted. Plasma concentrations were slightly higher in Japanese versus Caucasian men; these differences were not significant after adjustment for differences in body mass (clearance: approximately 1.2 ml/h/kg; volume of distribution at steady state: approximately 0.07 l/kg). The ex vivo endotoxin inhibitory activity of eritoran was similar in Japanese and Caucasian men. The data do not indicate any need for clinical dose adjustment for possible ethnic-based differences in drug distribution or metabolism.
- Subjects
CAUCASUS; INTRAVENOUS therapy; PHARMACOKINETICS; PHARMACODYNAMICS; LIPIDS; DRUG dosage; ENDOTOXINS; TOLL-like receptors; JAPANESE people; DISEASES
- Publication
Innate Immunity, 2012, Vol 18, Issue 6, p793
- ISSN
1753-4259
- Publication type
Article
- DOI
10.1177/1753425912441845