Bioavailability assessment of fexofenadine and montelukast in a fixed-dose combination tablet versus the components administered simultaneously

Introduction and Objectives: Allergic rhinitis is a condition with high global prevalence most effectively treated with antihistamines and antileukotrienes. This study aimed to evaluate the bioequivalence of fexofenadine and montelukast in a fixed-dose combination tablet versus the components administered simultaneously. Materials and Methods: An open, randomized, 2×2 crossover study was performed in 78 healthy volunteers. Fexofenadine–montelukast tablets containing 120 mg and 10 mg, respectively, were used as the test treatment, and 120 mg fexofenadine tablets and 10 mg montelukast tablets were used as the reference treatment. Concentrations of fexofenadine and montelukast in plasma were determined by protein precipitation and analysis by liquid chromatography/mass spectrometry or liquid chromatography tandem mass spectrometry. Results: The 90% confidence intervals (CIs) obtained for fexofenadine were 87.612–102.144 for area under the curve of the plasma concentration after administration to the last concentration (AUC0-t), 88.471–102.282 for the AUC of the plasma concentration extrapolated to infinity (AUC0–∞), and 91.413–108.544 for the maximum plasma concentration (Cmax). For montelukast, they were 96.418–108.416 for AUC0-t, 93.273–106.642 for AUC0-∞ and 94.749–110.178 for Cmax. The ratio and CIs of the values subjected to logarithmic transformation for each parameter were within the range of acceptability of 80%–125%, demonstrating the bioequivalence of the combined fixed-dose tablet to the components administered separately at the same doses. No adverse events were recorded during the study. Conclusions: This study has shown the bioequivalence of the combined fixed-dose tablet, which may be considered a new alternative for the treatment of allergic rhinitis (AU)

Efavirenz as a potential drug for the treatment of triple-negative breast cancers

Purpose In contrast to hormone receptor driven breast cancer, patients presenting with triple-negative breast cancer (TNBC) often have limited drug treatment options. Efavirenz, a non-nucleoside reverse transcriptase (RT) inhibitor targets abnormally overexpressed long interspersed nuclear element 1 (LINE-1) RT and has been shown to be a promising anticancer agent for treating prostate and pancreatic cancers. However, its effectiveness in treating patients with TNBC has not been comprehensively examined. Methods In this study, the effect of Efavirenz on several TNBC cell lines was investigated by examining several cellular characteristics including viability, cell division and death, changes in cell morphology as well as the expression of LINE-1. Results The results show that in a range of TNBC cell lines, Efavirenz causes cell death, retards cell proliferation and changes cell morphology to an epithelial-like phenotype. In addition, it is the first time that a whole-genome RNA sequence analysis has identified the fatty acid metabolism pathway as a key regulator in this Efavirenz-induced anticancer process. Conclusion In summary, we propose Efavirenz is a potential anti-TNBC drug and that its mode of action can be linked to the fatty acid metabolism pathway (AU)

Inhibidores de la PDE4: roflumilast / Phosphodiesterase-4 inhibitors: roflumilast

La enfermedad pulmonar obstructiva crónica (EPOC) es un término que engloba un grupo de trastornos caracterizados por la presencia de obstrucción crónica de las vías aéreas. Este amplio paraguas diagnóstico incluye varios fenotipos clínicos que se solapan y que responden de forma diferente a cada tipo de intervención terapéutica. Roflumilast es un fármaco perteneciente a la nueva clase terapéutica de los inhibidores de la fosfodiesterasa 4 (PDE4). Se puede considerar el primer fármaco desarrollado para el tratamiento de un fenotipo específico de la EPOC (EPOC asociada a bronquitis crónica). En modelos preclínicos, roflumilast ha mostrado una potente acción antiinflamatoria sobre una amplia variedad de células y mediadores inflamatorios, así como sobre otros mecanismos etiopatogénicos propios de la EPOC. El presente documento revisa la evidencia generada durante el desarrollo clínico de roflumilast , con un énfasis especial en los estudios que valoran el fármaco en el contexto similar a nuestra práctica clínica habitual (AU)

Chronic obstructive pulmonary disease (COPD) encompasses a group of diseases characterized by chronic airway obstruction. This broad diagnostic umbrella includes several clinical phenotypes that overlap and respond differently to each type of therapeutic intervent ion. Roflumilast is a drug belonging to the new therapeutic class of phosphyldiesterase-4 (PDE4) inhibitors and can be considered the first drug to be developed for a specific COPD phenotype (COPD associated with chronic bronchit is). In preclinical models, roflumilast has shown potent ant iinflammatory action against a wide variety of cells and inflammatory mediators, as well as against the etiopathogenic mechanisms of COPD. The present article reviews the evidence generated during the clinical development of roflumilast , with special emphasis on studies evaluating the drug in a context similar to that of routine clinical pract ice (AU)