The plasma and salivary disposition of closantel and rafoxanide were examined following intravenous administration in adult sheep. Two studies were conducted with rafoxanide at 7.5 mg/kg and 1 with closantel using 2 doses (5 and 15 mg/kg). The pharmacokinetic profile of both drugs in plasma were best described by a 2-compartmental model with 1st-order rate constants. Plasma disposition of closa...

We consider the possibility of free receptor (antigen/cytokine) levels rebounding to higher than the baseline level after one or more applications of an antibody drug using a target-mediated drug disposition model. Using geometry and dynamical systems analysis, we show that rebound will occur if and only if the elimination rate of the drug-receptor product is slower than the elimination rates o...

The model elimination calculus is a linear, refutationally complete calculus for first order clause logic. We show how to extend this calculus with aframeworkfor theory reasoning. Theory reasoning m~ans to separate the knowledge of a given domain or theory and treat it by special purpose inference rules. We present two versions of theory model elimination: the one is called total theory model e...

The purpose of these studies was to better understand the behavioral effects and pharmacokinetics of an i.v. bolus dose of (+)-methamphetamine [(+)-METH] in a rat model of (+)-METH abuse. We characterized the behavioral effects after increasing (+)-METH doses (0.1, 0.3, and 1.0 mg/kg) and the pharmacokinetics of (+)-METH (and its metabolite (+)-amphetamine [(+)-AMP)]) at the lowest and highest ...

BACKGROUND International financing for malaria increased more than 18-fold between 2000 and 2011; the largest source came from The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). Countries have made substantial progress, but achieving elimination requires sustained finances to interrupt transmission and prevent reintroduction. Since 2011, global financing for malaria has decl...

Levosimendan is a new drug for the treatment of decompensated heart failure. In previous studies, levosimendan has been shown to increase cardiac contractility through myofilament calcium sensitisation and induce peripheral and coronary vasodilation by opening ATP-sensitive potassium channels. The elimination half-life of levosimendan is approximately one hour in man. Preclinical studies have s...

The pyridoxal form of alanine aminotransferase from pig heart catalyzes the a,/? elimination reaction with 3chloro-L-alanine as the substrate to form equimolar amounts of pyruvate, ammonia, and chloride. The maximum rate of the a,/3 elimination reaction was 2.5 pmol/min/mg at pH 7.0 (25”(Z), approximately 0.5% that of the transamination reaction between L-alanine and 2-oxoglutarate. Time-depend...

The pyridoxal form of alanine aminotransferase from pig heart catalyzes the a,/? elimination reaction with 3chloro-L-alanine as the substrate to form equimolar amounts of pyruvate, ammonia, and chloride. The maximum rate of the a,/3 elimination reaction was 2.5 pmol/min/mg at pH 7.0 (25”(Z), approximately 0.5% that of the transamination reaction between L-alanine and 2-oxoglutarate. Time-depend...