Contribution of protein binding to the pharmacokinetics of the ghrelin receptor agonist TZP-101 in healthy volunteers and adults with symptomatic gastroparesis: two randomized, double-blind studies and a binding profile study.

Background And Objective: TZP-101 is a selective, small molecule ghrelin receptor agonist in clinical development for the treatment of gastric motility disorders. The objectives of this study was to assess pharmacokinetic parameters of TZP-101 after multiple- and single-dose administration to healthy subjects and patients with gastroparesis, respectively, and to determine the contribution of protein binding to its pharmacokinetic behaviour.

Methods: Pharmacokinetics following 30-minute intravenous infusions of single (160-600 microg/kg) doses of TZP-101 in patients with gastroparesis and multiple (80-600 mug/kg/day) doses of TZP-101 in healthy subjects were characterized.

Pharmacokinetics of novel atrial-selective antiarrhythmic agent vernakalant hydrochloride injection (RSD1235): influence of CYP2D6 expression and other factors.

Vernakalant hydrochloride injection (RSD1235) is a relatively atrial-selective antiarrhythmic agent that converts atrial fibrillation rapidly to sinus rhythm. The pharmacokinetics of vernakalant were explored in healthy volunteers and in patients with atrial fibrillation or atrial flutter in 4 clinical studies. Key pharmacokinetic parameters analyzed were the maximum plasma concentration and the area under the plasma concentration-time curve.

Synthesis and biological studies of novel 2-aminoalkylethers as potential antiarrhythmic agents for the conversion of atrial fibrillation.

A series of 2-aminoalkylethers prepared as potential antiarrhythmic agents is described. The present compounds are mixed sodium and potassium ion channel blockers and exhibit antiarrhythmic activity in a rat model of ischemia-induced arrhythmias. Structure-activity studies led to the identification of three compounds 5, 18, and 26, which were selected based on their particular in vivo electrophysiological properties, for studies in two canine atrial fibrillation (AF) models.

Comparison between capillary electrophoresis and high-performance liquid chromatography for the stereoselective analysis of carvedilol in serum.

A high-performance liquid chromatographic (HPLC) assay using a chiral stationary phase was developed and validated for the determination of carvedilol enantiomers in human serum and was compared with a previously developed capillary electrophoresis (CE) method. The CE and the HPLC assay were compared by analyzing a series of serum samples containing racemic carvedilol in different concentrations using the two methods. The concentrations obtained by the two assays were not found to be significantly different indicating that CE and HPLC are comparable in terms of reproducibility and precision for the stereoselective analysis of carvedilol in human serum.

Validation of a capillary electrophoresis assay for assessing the metabolic stability of verapamil in human liver microsomes.

A simple CE assay for the rapid determination of the in vitro metabolic stability of verapamil in human liver microsomes has been developed and validated. Verapamil was used as the prototype drug since it is extensively metabolized in human liver microsomes. The assay showed good intra- (CV < or = 10%) and interday (CV < or = 8%) reproducibility.