Pharmacokinetic analysis of nicotine and its metabolites (cotinine and trans-3'-hydroxycotinine) in male Sprague-Dawley rats following nose-only inhalation, oral gavage, and intravenous infusion of nicotine.

Nicotine is an alkaloid found in tobacco. Human exposure to nicotine primarily occurs through the use of tobacco products. To date, limited nicotine pharmacokinetic data in animals have been reported.

A randomized controlled laboratory study on the long-term effects of methylphenidate on cardiovascular function and structure in rhesus monkeys.

Background: Whether long-term methylphenidate (MPH) results in any changes in cardiovascular function or structure can only be properly addressed through a randomized trial using an animal model which permits elevated dosing over an extended period of time.

Methods: We studied 28 male rhesus monkeys (Macaca mulatta) approximately 7 years of age that had been randomly assigned to one of three MPH dosages: vehicle control (0 mg/kg, b.i.

Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes.

Of the 34 FDA approved oral small-molecule kinase inhibitors (KI), 23 (68%) have warnings for hepatotoxicity in product labeling. To better understand the mechanisms of KI hepatotoxicity and whether such effects can be predicted, we examined 34 KIs for cytotoxicity in primary rat and human hepatocytes. The hepatocytes were treated with KIs at ten concentrations normalized to maximal therapeutic blood levels (Cmax).