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Pharmaceutics. 2010 Mar;2(1):18-29.

Determination of the Pharmacokinetics and Oral Bioavailability of Salicylamine, a Potent γ-Ketoaldehyde Scavenger, by LC/MS/MS.

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1
Division of Clinical Pharmacology, Departments of Pharmacology, Medicine, and Pathology, Vanderbilt University, Nashville, TN, USA; irene.zagol@vanderbilt.edu (I.A.Z.-I.); elena.matafonova@vanderbilt.edu (E.M.); venkataraman.amarnath@vanderbilt.edu (V.A.); christopher.l.bodine@vanderbilt.edu (C.L.B.); olivier.boutaud@vanderbilt.edu (O.B.); john.oates@vanderbilt.edu (J.A.O.); jack.roberts@vanderbilt.edu (L.J.R.).

Abstract

Levels of reactive γ-ketoaldehydes derived from arachidonate increase in diseases associated with inflammation and oxidative injury. To assess the biological importance of these γ-ketoaldehydes, we previously identified salicylamine as an effective γ-ketoaldehyde scavenger in vitro and in cells. To determine if salicylamine could be administered in vivo, we developed an LC/MS/MS assay to measure salicylamine in plasma and tissues. In mice, half-life (t(1/2)) was 62 minutes. Drinking water supplementation (1-10 g/L) generated tissue concentrations (10-500 μM) within the range previously shown to inhibit γ-ketoaldehydes in cells. Therefore, oral administration of salicylamine can be used to assess the contribution of γ-ketoaldehydes in animal models of disease.

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