Randomised, crossover clinical trial, in healthy volunteers, to compare the systemic availability of two topical intranasal budesonide formulations

Background: Budesonide has a long history as intranasal drug, with many marketed products. Efforts should be made to demonstrate the therapeutic equivalence and safety comparability between them. Given that systemic availability significantly varies from formulations, the clinical comparability of diverse products comes to be of clinical interest and a regulatory requirement. The aim of the present study was to compare the systemic availability, pharmacodynamic effect, and safety of two intranasal budesonide formulations for the treatment of rhinitis. Methods: Eighteen healthy volunteers participated in this randomised, controlled, crossover, clinical trial. On two separated days, subjects received a single dose of 512 mu g budesonide (4 puffs per nostril) from each of the assayed devices (Budesonida nasal 64 (R), Aldo-Union, Spain and Rhinocort 64 (R), AstraZeneca, Spain). Budesonide availability was determined by the measurement of budesonide plasma concentration. The pharmacodynamic effect on the hypothalamic-adrenal axis was evaluated as both plasma and urine cortisol levels. Adverse events were tabulated and described. Budesonide availability between formulations was compared by the calculation of 90% CI intervals of the ratios of the main pharmacokinetic parameters describing budesonide bioavailability. Plasma cortisol concentration-time curves were compared by means of a GLM for Repeated Measures. Urine cortisol excretion between formulations was compared through the Wilcoxon's test. Results: All the enroled volunteers successfully completed the study. Pharmacokinetic parameters were comparable in terms of AUC(t) (2.6 +/- 1.5 vs 2.2 +/- 0.7), AUCi (2.9 +/- 1.5 vs 2.4 +/- 0.7), t(max) (0.4 +/- 0.1 vs 0.4 +/- 0.2), C(max)/AUC(i) (0.3 +/- 0.1 vs 0.3 +/- 0.0), and MRT (5.0 +/- 1.4 vs 4.5 +/- 0.6), but not in the case of C(max) (0.9 +/- 0.3 vs 0.7 +/- 0.2) and t(1/2) (3.7 +/- 1.8 vs 2.9 +/- 0.4). The pharmacodynamic effects, measured as the effect over plasma and urine cortisol, were also comparables between both formulations. No severe adverse events were reported and tolerance was comparable between formulations. Conclusion: The systemic availability of intranasal budesonide was comparable for both formulations in terms of most pharmacokinetic parameters. The pharmacodynamic effect on hypothalamic-pituitary-adrenal axis was also similar. Side effects were scarce and equivalent between the two products. This methodology to compare different budesonide-containing devices is reliable and easy to perform, and should be recommended for similar products intented to be marketed or already on the market.

Fiabilidad de diferentes pruebas que se utilizan para evaluar el riesgo de lesión del miembro inferior en mujeres deportistas

233 p. : il. + anexo (247 p.)

Impact of Cyberprogram 2.0 on Different Types of School Violence and Aggressiveness

Some antibullying interventions have shown positive outcomes with regard to reducing violence. The aim of the study was to experimentally assess the effects on school violence and aggressiveness of a program to prevent and reduce cyberbullying. The sample was comprised of a randomly selected sample of 176 adolescents (93 experimental, 83 control), aged 13-15 years. The study used a repeated measures pre-posttest design with a control group. Before and after the program, two assessment instruments were administered: the "Cuestionario de Violencia Escolar-Revisado" (CUVE-R [School Violence Questionnaire- Revised]; Alvarez Garcia et al., 2011) and the "Cuestionario de agresividad premeditada e impulsiva" (CAPI-A [Premeditated and Impulsive Aggressiveness Questionnaire]; Andreu, 2010). The intervention consisted of 19 one-hour sessions carried out during the school term. The program contains 25 activities with the following objectives: (1) to identify and conceptualize bullying/cyberbullying; (2) to analyze the consequences of bullying/cyberbullying, promoting participants' capacity to report such actions when they are discovered; (3) to develop coping strategies to prevent and reduce bullying/cyberbullying; and (4) to achieve other transversal goals, such as developing positive variables (empathy, active listening, social skills, constructive conflict resolution, etc.). The pre-posttest ANCOVAs confirmed that the program stimulated a decrease in: (1) diverse types of school violence teachers' violence toward students (ridiculing or publicly humiliating students in front of the class, etc.); students' physical violence (fights, blows, shoves... aimed at the victim, or at his or her property, etc.); students' verbal violence (using offensive language, cruel, embarrassing, or insulting words... toward classmates and teachers); social exclusion (rejection or exclusion of a person or group, etc.), and violence through Information and Communication Technologies (ICT; violent behaviors by means of electronic instruments such as mobile phones and the Internet); and (2) premeditated and impulsive aggressiveness. Pre-posttest MANCOVA revealed differences between conditions with a medium effect size. This work contributes an efficacious intervention tool for the prevention and reduction of peer violence. The conclusions drawn from this study have interesting implications for educational and clinical intervention.