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

Pharmaceutics

Irene Zagol-Ikapitte²  Elena Matafonova²  Venkataraman Amarnath²  Christopher L. Bodine²  Olivier Boutaud²  Rommel G. Tirona¹  John A. Oates²  L. JacksonRoberts² 

[1] Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada; E-Mail:;Division of Clinical Pharmacology, Departments of Pharmacology, Medicine, and Pathology, Vanderbilt University, Nashville, TN, USA; E-Mails:

关键词: levuglandins;    isoketals;    aldehydes;    scavengers;    oxidative stress;    inflammation;    lipid peroxidation;    bioavailability;    pharmacokinetics;   

DOI  :  10.3390/pharmaceutics2010018

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.