A blinded comparison of fluticasone propionate with budesonide via powder devices in adult patients with moderate-to-severe asthma: a clinical evaluation

In Vitro and in vivo data have demonstrated that there are detectable differences between inhaled corticosteroids commonly used to treat asthma. However, controversy still remains as to whether these differences translate into clinical benefits. This 12-week, international, randomized, doubleblind, parallel-group study was undertaken to compare the efficacy and safety of fluticasone propionate (FP) 800 μg daily, administered as a powder via the Diskhaler®, and budesonide (BUD) 1600 μg daily, administered using the Turbuhaler®, in adult patients with moderate-tosevere asthma. A total of 518 patients participated in the study, 256 of whom received FP and 262 BUD. Assessment of mean morning peak expiratory flow (PEF) over the 12-week treatment period revealed a statistically significant difference in efficacy between FP 800 μg daily and BUD 1600 μg daily in favour of FP (p = 0.003), with an overall improvement of 20.9 l/min with FP compared with 12.4 l/min on BUD. Statistically significant differences in favour of FP were seen over the 12 weeks for mean evening PEF (p = 0.04), diurnal PEF variation (p = 0.03) and percentage predicted PEF (p = 0.003), as well as forced expiratory volume (p = 0.008), forced vital capacity (p = 0.02) and PEF (p = 0.005) measured at clinic visits. The median percentage of symptom-free nights increased over the 12-week study period in both treatment groups, with similar changes seen for the median percentage of days with symptom score < 2, rescue medication use and exacerbations of asthma. The incidence of adverse events was found to be comparable in the two treatment groups. The geometric mean ratios of serum cortisol levels were found to be 1.03 for FP, indicating no mean hypothalamic-pituitary-adrenal axis suppression from baseline, and 0.93 for BUD (p = 0.0002 compared with FP). In summary, FP 800 μg daily showed a greater efficacy/safety ratio in the treatment of moderate-to-severe asthma than BUD 1600 μg daily

In Silico Analysis Identifies Intestinal Transit as a Key Determinant of Systemic Bile Acid Metabolism

Bile acids fulfill a variety of metabolic functions including regulation of glucose and lipid metabolism. Since changes of bile acid metabolism accompany obesity, Type 2 Diabetes Mellitus and bariatric surgery, there is great interest in their role in metabolic health. Here, we developed a mathematical model of systemic bile acid metabolism, and subsequently performed in silico analyses to gain quantitative insight into the factors determining plasma bile acid measurements. Intestinal transit was found to have a surprisingly central role in plasma bile acid appearance, as was evidenced by both the necessity of detailed intestinal transit functions for a physiological description of bile acid metabolism as well as the importance of the intestinal transit parameters in determining plasma measurements. The central role of intestinal transit is further highlighted by the dependency of the early phase of the dynamic response of plasma bile acids after a meal to intestinal propulsion