Racecadotril is a guideline-recommended option for the treatment of acute diarrhea in children but existing guidelines and previous reviews of the field are based on a small fraction of published ...evidence. Therefore, we have performed a systematic search for randomized controlled trials evaluating racecadotril as add-on or in comparison to other treatments.
A search was performed in PubMed, Scopus and Google Scholar without limits about country of origin or reporting language. A meta-analysis was conducted for the five most frequently used efficacy parameters.
We have retrieved 58 trials, from nine countries including six in comparison to placebo, 15 in comparison to various active treatments and 41 as add-on to various standard treatments (some multi-armed studies allowing more than one comparison). Trials used 45 distinct efficacy parameters, most often time to cure, % of cured children after 3 days of treatment, global efficacy and number of stools on second day of treatment. Racecadotril was superior to comparator treatments in outpatients and hospitalized patients with a high degree of consistency as confirmed by meta-analysis for the five most frequently used outcome parameters. For instance, it reduced time to cure from 106.2 h to 78.2 h (mean reduction 28.0 h; P < 0.0001 in 24 studies reporting on this parameter). Tolerability of racecadotril was comparable to that of placebo (10.4% vs. 10.6% adverse events incidence) or that of active comparator treatments other than loperamide (2.4% in both groups).
Based on a comprehensive review of the existing evidence, we conclude that racecadotril is more efficacious than other treatments except for loperamide and has a tolerability similar to placebo and better than loperamide. These findings support the use of racecadotril in the treatment of acute diarrhea in children.
Ambroxol relieves cough symptoms based on its secretagogue, anti-inflammatory, anti-oxidant, anti-bacterial, anti-viral, immunomodulatory and local anesthetic effects. The present study was designed ...to explore differential patient profiles and efficacy against acute respiratory symptoms of four formulations registered as over-the-counter medicines.
Nine hundred sixty-five pharmacy customers purchasing one of four branded ambroxol formulations (extended release capsules, adult syrup, pediatric syrup and soft pastilles) filled a questionnaire including a patient-adapted version of the Bronchitis Severity Scale, several questions on degree of impairment by acute cough, time to onset of symptom relief and duration of treatment. Data on pediatric syrup users were entered by their parents. Based on the exploratory character of the study, no hypothesis-testing statistical analysis was applied.
Users of the pediatric syrup and the pastilles reported somewhat less severe baseline symptoms. The patient-adapted Bronchitis Severity Scale proved feasible as a self-administered tool. Among BSS items, ambroxol formulations improved chest pain while coughing to the largest and sputum to smallest degree (- 75% vs. -40%). Reported efficacy was comparable among formulations with minor differences in favor of the pediatric syrup. Time to onset of symptom relief was less than 60 min in more than 90% of patients and occurred prior to known systemic t
. Time to onset was the parameter with the greatest differences between formulations, being reported fastest with pastilles and pediatric syrup and, as expected, slowest with extended release capsules. All ambroxol formulations were well tolerated.
We conclude that over-the-counter formulations of ambroxol exhibit comparable user profiles and efficacy. Differences in speed of onset of symptom relief may involve not only those in systemic pharmacokinetics but also local anesthetic effects of immediate release formulations. Differences between pediatric and adult syrup may in part reflect reporting bias.
We could recently demonstrate an important role of receptor interacting protein-2 (RIP2), an activator of nuclear factor kappa B (NF-κB) and a target of activated receptors of the tumor necrosis ...factor receptor (TNFR) type, in myogenic differentiation and regeneration. Here, we analyze a potential role of TNFR associated factor 6 (TRAF6), which also associates with the cytoplasmic domain of TNFR type, but also IL-1-R and TLR type receptors, and activates NF-κB, in these processes. Specifically, we show that during myogenic differentiation
in vitro,
traf6 gene expression is downregulated in normal myoblasts, but not in rhabdomyosarcoma cells, suggesting a role of the TRAF6 protein in this process. Inhibition of
traf6 expression using specific siRNAs led to an inhibition of both myoblast proliferation and differentiation, whereas inhibition of the TRAF6 effector NF-κB alone in our system only blocked proliferation. Finally, we demonstrate that the
traf6 gene is downregulated in skeletal muscle tissue of the dystrophic
mdx mouse. Taken together, these data argue for a role of TRAF6 in the regulation of skeletal muscle differentiation and regeneration.
Rapid onset of analgesic action is linked with rapid absorption of analgesics (high maximum concentration Cmax and short time to maximum concentration tmax). After overnight fasting, ibuprofen ...lysinate reaches higher peak plasma levels (Cmax) earlier than ibuprofen acid (tmax) with comparable exposure (area under the plasma concentration–time curve AUC); however, subjects usually take ibuprofen with or within a short time of a meal. Therefore, pharmacokinetic (PK) studies under fed conditions may better characterize properties under real‐life conditions. We investigated a new fixed‐dose combination (FDC) of ibuprofen acid 400 mg and caffeine 100 mg in 2 single‐dose, randomized, crossover PK studies in healthy subjects (both N = 36). The FDC was compared with ibuprofen 400 mg as acid and as lysinate after an overnight fast in Study 1, and with ibuprofen lysinate after a meal in Study 2. After fasting, results for ibuprofen in the FDC were comparable with those from ibuprofen acid alone. Caffeine did not affect the Cmax, tmax, and AUC. As expected, a higher Cmax and shorter tmax were observed with ibuprofen lysinates vs the FDC. Compared with administration after fasting, Cmax and tmax for ibuprofen lysinate administered postprandially were markedly different, while with FDC, these parameters were less sensitive to food intake. Taken after a meal, ibuprofen in the FDC reached tmax earlier than ibuprofen lysinate (median 1.25 vs 1.63 hours), and Cmax was approximately 13% higher, with comparable AUC, suggesting that the profile of ibuprofen was in favor of the FDC compared with ibuprofen lysinate. Thus, under real‐life conditions, ibuprofen lysinate had no PK advantage over the FDC. All preparations were well tolerated.
Summary
Aim
The aim of this study was to explore factors affecting efficacy of treatment of common cold symptoms with an over‐the‐counter ibuprofen/pseudoephedrine combination product.
Methods
Data ...from an anonymous survey among 1770 pharmacy customers purchasing the combination product for treatment of own common cold symptoms underwent post‐hoc descriptive analysis. Scores of symptoms typically responsive to ibuprofen (headache, pharyngeal pain, joint pain and fever), typically responsive to pseudoephedrine (congested nose, congested sinus and runny nose), considered non‐specific (sneezing, fatigue, dry cough, cough with expectoration) and comprising all 11 symptoms were analysed. Multiple regression analysis was applied to explore factors associated with greater reduction in symptom intensity or greater probability of experiencing a symptom reduction of at least 50%.
Results
After intake of first dose of medication, typically ibuprofen‐sensitive, pseudoephedrine‐responsive, non‐specific and total symptoms were reduced by 60.0%, 46.3%, 45.4% and 52.8%, respectively. A symptom reduction of at least 50% was reported by 73.6%, 55.1%, 50.9% and 61.6% of participants, respectively. A high baseline score was associated with greater reductions in symptom scores but smaller probability of achieving an improvement of at least 50%. Across both multiple regression approaches, two tablets at first dosing were more effective than one and (except for ibuprofen‐sensitive symptoms) starting treatment later than day 2 of the cold was generally less effective.
Discussion and Conclusions
Efficacy of an ibuprofen/pseudoephedrine combination in the treatment of common cold symptoms was dose‐dependent and greatest when treatment started within the first 2 days after onset of symptoms.
PDF
