Tissue Distribution and Elimination of Isavuconazole following Single and Repeat Oral-Dose Administration of Isavuconazonium Sulfate to Rats.

Quantitative whole-body autoradiography was used to assess the distribution and tissue penetration of isavuconazole in rats following single and repeated oral-dose administration of radiolabeled isavuconazonium sulfate, the prodrug of isavuconazole. Following a single-dose administration of radiolabeled isavuconazonium sulfate (labeled on the active moiety), radioactivity was detectable within 1 h postdose in 56 of 65 tissue/fluid specimens. The highest maximum concentrations () were observed in bile and liver (66.

Translational science approach for assessment of cardiovascular effects and proarrhythmogenic potential of the beta-3 adrenergic agonist mirabegron.

Introduction: Translational assessment of cardiac safety parameters is a challenge in clinical development of beta-3 adrenoceptor agonists. The preclinical tools are presented that were used for assessing human safety for mirabegron.

Methods: Studies were performed on electrical conductance at ion channels responsible for cardiac repolarization (I, I, I, I, and I), on QT-interval, subendocardial APD, T interval, and arrhythmia's in ventricular dog wedge tissue in vitro and on cardiovascular function (BP, HR, and QT) in conscious dogs.

Effect of mirabegron on plasma gonadotropic and steroidal hormone levels in rats after two weeks of oral administration.

The effects of mirabegron on plasma gonadotropic and steroidal hormone levels in rats were investigated, when administered orally once daily for two weeks to male and female rats at doses of 10, 30, and 100 mg/kg/day, in order to elucidate a potential mechanism for findings in the reproductive system observed in toxicity studies in rats. Significantly decreased body weight gain and food consumption were observed in males and females at 100 mg/kg/day on Days 1 to 4 of dosing. A significantly prolonged estrous interval was observed in females at 100 mg/kg/day and increased liver weights were noted in females at 30 mg/kg/day or greater.

Vernakalant selectively prolongs atrial refractoriness with no effect on ventricular refractoriness or defibrillation threshold in pigs.

Vernakalant is a novel antiarrhythmic agent that has demonstrated clinical efficacy for the treatment of atrial fibrillation. Vernakalant blocks, to various degrees, cardiac sodium and potassium channels with a pattern that suggests atrial selectivity. We hypothesized, therefore, that vernakalant would affect atrial more than ventricular effective refractory period (ERP) and have little or no effect on ventricular defibrillation threshold (DFT).

Comparative efficacies of telavancin and vancomycin in preventing device-associated colonization and infection by Staphylococcus aureus in rabbits.

Telavancin is an investigational lipoglycopeptide antibiotic that is active against gram-positive pathogens. In an in vivo rabbit model, subtherapeutic (15-mg/kg) and therapeutic (30- or 45-mg/kg) doses of telavancin were demonstrated to be noninferior and superior to vancomycin (20 mg/kg), respectively, for preventing subcutaneous implant colonization and infection by Staphylococcus aureus.