In Vitro-In Vivo Correlations Observed With Indacaterol-Based Formulations Delivered with the Breezhaler®.

Background: Establishing robust in vitro-in vivo correlations (IVIVC) between aerosol performance, pharmacokinetics, and clinical efficacy is critical in developing bioequivalent drug-device combination products. Recent studies have demonstrated that realistic throat models tested under realistic test conditions may provide good IVIVC with respect to total lung deposition.

Methods: The Alberta idealized throat (AIT) model was utilized with mean peak inspiratory flow rates determined from patient breathing studies.

Effect of dual bronchodilation with QVA149 on cardiac safety in healthy volunteers.

Objectives: QVA149 is a dual bronchodilator, containing a fixed-dose combination of the long-acting β2-agonist indacaterol and long-acting muscarinic antagonist glycopyrronium, for the treatment of chronic obstructive pulmonary disease (COPD). Here we assess the potential of QVA149 (440/200 μg) at 4-fold the therapeutic dose for causing cardiac pharmacodynamic (PD) effects.

Methods: This double-blind, randomized study estimated the time-matched largest heart rate (HR) change and average HR change (over 24 hours) from baseline for QVA149 vs.

Dietary supplementation with S-adenosyl methionine was associated with protracted reduction of seizures in a line of transgenic mice.

Transgenic mice, although useful for analyses of gene function, can present unanticipated phenotypic manifestations, including behavioral problems, that may not be directly associated with the gene of interest but rather due to the complex interplay inherent in genomes. These unexpected events can present unique insight into gene function, leading to an advantage in some situations, yet in others can confound interpretation and compromise usefulness of the transgenic line. Here we document that short-term supplementation with S-adenosyl methionine (SAM)--a nutriceutical known to regulate neurotransmitter levels, improve working memory, and reduce aggression--reduced handling- and startling-induced seizures that otherwise precluded behavioral analyses in a transgenic line.

A dose-ranging study of indacaterol in obstructive airways disease, with a tiotropium comparison.

This dose-ranging study assessed the bronchodilator efficacy and tolerability of indacaterol, a novel once-daily inhaled beta2-agonist, in subjects clinically diagnosed with COPD. Comparative data with tiotropium were collected. In the double-blind, core period of the study, 635 subjects with COPD (prebronchodilator FEV(1)40% of predicted and > or =1.