Improvement in the Oral Bioavailability and Efficacy of New Ezetimibe Formulations-Comparative Study of a Solid Dispersion and Different Micellar Systems.

Ezetimibe (EZ) is a poorly water-soluble drug with low bioavailability. Strategies such as solid dispersions (SD) and micellar systems (MS) were developed to identify the most effective drug delivery formulations with the highest oral bioavailability, and to improve their lipid-lowering effect. The EZ formulations were prepared with different proportions of Kolliphor® RH40 as a surfactant (1:0.25, 1:0.5 and 1:0.75) and croscarmellose as a hydrophilic carrier. These excipients, and the addition of microcrystalline cellulose during the production process, led to significant improvements in the dissolution profiles of MS. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) revealed an amorphous form of ezetimibe with different semicrystalline states of microcrystalline cellulose for MS-I (1:0.75) and MS-II (1:0.75). Pharmacokinetic analysis after administration of MS-II (1:0.75) demonstrated a 173.86% increase in maximum plasma concentration (Cmax) and a 142.99% increase in oral bioavailability compared to EZ raw material (EZ-RM). Efficacy studies with the micellar system MS-II (1:0.75) in rats with hyperlipidemia showed that total cholesterol, triglycerides and high-density lipoprotein were reduced to normal levels and revealed improvements in low-density lipoprotein, aspartate and alanine aminotransferase. The improvement in the dissolution rate with micellar systems increases bioavailability and enhances the anti-hyperlipidemic effect of EZ.

Improvement of the pharmacokinetic/pharmacodynamic relationship in the treatment of invasive aspergillosis with voriconazole. Reduced drug toxicity through novel rapid release formulations.

Voriconazole (VCZ) is currently the first-line treatment for invasive aspergillosis, although the doses are limited by its poor solubility and high hepatic toxicity. The aim of this study was to develop a solid self-dispersing micellar system of VCZ to improve the pharmacokinetic/pharmacodynamic (PK/PD) relationship and reduce hepatotoxicity. In this work, solid micellar systems of VCZ are formulated with different polysorbate 80 ratios using mannitol as a hydrophilic carrier. The novel micellar systems were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and dissolution studies. Self-dispersing micellar systems reduced VCZ crystallinity, leading to an improvement in its dissolution rate. The in vitro susceptibility test also revealed that the most common microorganisms in invasive aspergillosis exhibited low minimum inhibitory concentration (MIC) values for micellar systems. Pharmacokinetic studies indicated an improvement in bioavailability for MS-1:3:0.05, and changes in its biodistribution to different organs. MS-1:3:0.05 showed an increased concentration in lungs and a significant decrease in VCZ accumulated in the liver.

Efectividad de un protocolo de ahorro de transfusión en la disminución de consumo de hematíes en cirugía protésica / Effectiveness of a patient blood management protocol on reduction of allogeneic red blood cell transfusions in orthopedic surgery

Antecedentes y objetivos: Los programas de ahorro de transfusión disminuyen el consumo de concentrados de hematíes en cirugía protésica. Se evalúa la efectividad de un protocolo basado en el Consenso de Sevilla en la disminución de la tasa transfusional y se propone una ecuación predictiva en cirugía de rodilla. Pacientes y métodos: Estudio de cohortes en pacientes sometidos a prótesis de rodilla y cadera en 2014 y 2015 en el Hospital Comarcal de l'Alt Penedès (HCAP). Pacientes con hemoglobina (Hb) entre 10 y 13g/dl se clasificaron en anemia con o sin déficit de hierro y recibieron hierro o combinación de hierro y eritropoyetina. El día de la cirugía se administró ácido tranexámico, al día siguiente se midió la caída de Hb y durante su estancia los requerimientos y el dintel transfusional. Resultados: El estudio incluyó 334 pacientes. El protocolo disminuyó la tasa de transfusión del 41,5 al 14,8%. En cirugía de cadera los pacientes transfundidos fueron mayores, con mayor porcentaje de comorbilidad y uso de anticoagulantes y menor Hb preoperatoria. El ácido tranexámico no se asoció a disminución del sangrado. En cirugía de rodilla, el análisis multivariante mostró que la administración de ácido tranexámico fue la variable que más disminuyó el riesgo de transfusión, seguido de valores de Hb preoperatoria más altos. La ecuación resultante predice la tasa transfusional, con una sensibilidad del 55% y una especificidad del 95,7%. Conclusión: La implantación del programa disminuyó la tasa transfusional. La efectividad de ácido tranexámico varía según la artroplastia. El uso conjunto de hierro y eritropoyetina recombinante humana es necesario para mejorar la Hb

Background and objectives: Patient blood management in orthopaedic surgery reduces transfusion risk. The best protocol is unknown. The effectiveness of a protocol based on the Seville Consensus on the reduction of transfusion risk is evaluated and a predictive transfusion equation is proposed in knee surgery. Patients and methods: Cohort study in patients undergoing knee and hip arthroplasty from January 2014 to December 2015 at a second level complexity hospital in Vilafranca del Penedès (Barcelona). Patients with Hb between 10 and 13g/dL were classified as anaemic with or without iron deficiency and received iron or combination of iron and erythropoietin. On the day of surgery, tranexamic acid was administered, the Hb drop was measured the next day and the requirements and the transfusion lintel were measured during the stay. Results: A total of 334 patients were included in the study. The implementation of the programme decreased the transfusion risk from 41.5% to 14.8% at the end of the study. In hip surgery, transfused patients were significantly older, sicker and with lower preoperative Hb. Tranexamic acid did not decrease bleeding. In knee surgery, the administration of tranexamic acid was the variable that most decreased the transfusion risk followed by a high preoperative Hb. The equation predicts transfusion risk with a sensitivity of 55% and specificity of 95.7%. Conclusion: The implementation of the programme reduces transfusion risk. The effectiveness of tranexamic acid varies according to surgery site. The use of iron and recombinant human erythropoietin is necessary to improve Hb

Effectiveness of a patient blood management protocol on reduction of allogeneic red blood cell transfusions in orthopedic surgery. / Efectividad de un protocolo de ahorro de transfusión en la disminución de consumo de hematíes en cirugía protésica.

BACKGROUND AND OBJECTIVES: Patient blood management in orthopaedic surgery reduces transfusion risk. The best protocol is unknown. The effectiveness of a protocol based on the Seville Consensus on the reduction of transfusion risk is evaluated and a predictive transfusion equation is proposed in knee surgery. PATIENTS AND METHODS: Cohort study in patients undergoing knee and hip arthroplasty from January 2014 to December 2015 at a second level complexity hospital in Vilafranca del Penedès (Barcelona). Patients with Hb between 10 and 13g/dL were classified as anaemic with or without iron deficiency and received iron or combination of iron and erythropoietin. On the day of surgery, tranexamic acid was administered, the Hb drop was measured the next day and the requirements and the transfusion lintel were measured during the stay. RESULTS: A total of 334 patients were included in the study. The implementation of the programme decreased the transfusion risk from 41.5% to 14.8% at the end of the study. In hip surgery, transfused patients were significantly older, sicker and with lower preoperative Hb. Tranexamic acid did not decrease bleeding. In knee surgery, the administration of tranexamic acid was the variable that most decreased the transfusion risk followed by a high preoperative Hb. The equation predicts transfusion risk with a sensitivity of 55% and specificity of 95.7%. CONCLUSION: The implementation of the programme reduces transfusion risk. The effectiveness of tranexamic acid varies according to surgery site. The use of iron and recombinant human erythropoietin is necessary to improve Hb.

Eficiencia en la prescripción de medicamentos: impacto de un programa de intercambio terapéutico / The efficiency of drug prescription: impact of a therapeutic exchange program

Objetivo Evaluar el impacto de un programa de intercambio terapéutico a omeprazol de los inhibidores de la bomba de protones (IBP).Método Ensayo comunitario que compara el impacto de un programa de intercambio terapéutico en los equipos de atención primaria de una comarca respecto a la no aplicación en una comarca control. Se incluyó a los pacientes con prescripción de un IBP entre mayo de 2008 y junio de 2009. La intervención consistió en sesiones educativas y facilitar a cada médico (n=68) los pacientes con un IBP que pudiera cambiarse a omeprazol. Se obtuvo información de la historia clínica (IBP prescrito, equipo de atención primaria) y de la aplicación de farmacia (coste de la dosis diaria definida de los IBP). A partir del riesgo relativo (RR) se comparó el porcentaje de intercambio terapéutico en cada comarca antes y después de la intervención. También se calculó el porcentaje de omeprazol al final de cada periodo de estudio y los cambios en los costes en IBP. Resultados Hubo más intercambios terapéuticos en el grupo de intervención (RR: 4,2; intervalo de confianza del 95% [IC95%]:3,1-5,8) respecto al control (RR: 1,8; IC95%:1,2-2,6). En el grupo de intervención, el porcentaje de pacientes con omeprazol pasó del 86,2% al 89,3%, y en el control del 84,3% al 84,7%. El coste del grupo IBP disminuyó un 7,6% en el grupo de intervención y aumentó un 2,0% en el control. Conclusiones El programa de intercambio terapéutico se ha mostrado efectivo. Se trata de una intervención sencilla, capaz de modificar las prescripciones y reducir sus costes (AU)

Objective To assess the impact of substituting proton pump inhibitors (PPI) for omeprazole. Method We performed a community trial of the impact of a therapeutic exchange program in the primary care teams of a region compared with non-implementation in a control region. The study included patients prescribed a PPI between May 2008 and June 2009. The intervention consisted of providing educational sessions to physicians (n=68), as well as a list of patients receiving a PPI who were suitable for therapeutic exchange. Information was gathered from medical records (PPI prescribed, primary care team) and the pharmacy database (cost of defined daily doses of the PPI). The percentage of therapeutic exchange in each region before and after the intervention was compared through relative risk (RR). The percentage of omeprazole at the end of each study period and changes in PPI costs were also calculated. Results Therapeutic exchange was higher in the intervention group (RR: 4.2; 95%CI: 3.1-5.8) than in the control group (RR: 1.8; 95%CI: 1.2-2.6). The percentage of patients prescribed omeprazole increased from 86.2% to 89.3% in the intervention region and from 84.3% to 84.7% in the control region. The total cost of the PPI group decreased by 7.6% in the intervention region and increased by 2.0% in the control group. Conclusions This study demonstrates the effectiveness of the therapeutic exchange program. This is a simple intervention that is able to modify prescription and reduce its costs (AU)

[The efficiency of drug prescription: impact of a therapeutic exchange program]. / Eficiencia en la prescripción de medicamentos: impacto de un programa de intercambio terapéutico.

OBJECTIVE: To assess the impact of substituting proton pump inhibitors (PPI) for omeprazole. METHOD: We performed a community trial of the impact of a therapeutic exchange program in the primary care teams of a region compared with non-implementation in a control region. The study included patients prescribed a PPI between May 2008 and June 2009. The intervention consisted of providing educational sessions to physicians (n=68), as well as a list of patients receiving a PPI who were suitable for therapeutic exchange. Information was gathered from medical records (PPI prescribed, primary care team) and the pharmacy database (cost of defined daily doses of the PPI). The percentage of therapeutic exchange in each region before and after the intervention was compared through relative risk (RR). The percentage of omeprazole at the end of each study period and changes in PPI costs were also calculated. RESULTS: Therapeutic exchange was higher in the intervention group (RR: 4.2; 95%CI: 3.1-5.8) than in the control group (RR: 1.8; 95%CI: 1.2-2.6). The percentage of patients prescribed omeprazole increased from 86.2% to 89.3% in the intervention region and from 84.3% to 84.7% in the control region. The total cost of the PPI group decreased by 7.6% in the intervention region and increased by 2.0% in the control group. CONCLUSIONS: This study demonstrates the effectiveness of the therapeutic exchange program. This is a simple intervention that is able to modify prescription and reduce its costs.

Effects of a high-fiber diet on symptoms of irritable bowel syndrome: a randomized clinical trial.

OBJECTIVE: We investigated the effects of dietary fiber on symptoms of irritable bowel syndrome. METHODS: A single-blind randomized clinical trial was designed. Fifty-six subjects with irritable bowel syndrome were prospectively and randomly assigned to one of two groups: group 1 received a diet containing 10.4 g/d of fiber and group 2 received a diet containing 30.5 g/d of fiber. Patients' body weights, nutritional intakes as assessed with 3-d written food records, and symptom scores were assessed at baseline and at 3 mo. RESULTS: There were no dropouts during the study. Total energy intake and the distribution of macronutrients were not significantly different between groups. Total dietary fiber intake did not reach recommended levels in either group but was higher in group 2 than in group 1 (25.95 +/- 2.12 g/d versus 6.06 +/- 2.7 g/d, P < 0.05). Initial fiber intake did not differ significantly between groups. Pain scores, bowel scores, and general scores improved in both groups (from baseline to 3 mo), and no significant differences were detected between groups. CONCLUSIONS: A modest fiber intake in patients with irritable bowel syndrome relieved symptoms, but this therapeutic benefit of fiber may have been due to a placebo effect because the results were similar in the low-fiber group.

Effect of soluble fiber intake in lipid and glucose levels in healthy subjects: a randomized clinical trial.

OBJECTIVE: The aim of our work was to carry out a randomized clinical trial with two diets, one enriched in fiber (total fiber 30 g and soluble fiber 4 g) to investigate the effect on lipid and glucose levels in healthy subjects. RESEARCH DESIGN AND METHODS: Fifty-three subjects were prospectively randomized to two groups (see Table 1). Group I received a diet with 10.4 g of fiber given as 1.97 g soluble fiber (pectins, gums and mucilages) and 8.13 g of insoluble fiber (hemicelullose, cellulose and lignins) and Group II received a diet with 30.5 g of fiber of which 4.11 g were soluble fiber and 25.08 g insoluble fiber. Prospective serial assessment of weight and nutritional intake (3 days written food records) were made. These determinations were performed at baseline and at 3 months. All enrolled subjects underwent the following examinations; fasting blood samples were drawn for measurement of total cholesterol, triglyceride concentrations and other lipid fractions, low density lipoprotein (LDL-cholesterol), high density lipoprotein (HDL-cholesterol), glucose, and insulin. RESULTS: Total calorie and fat consumption were lower than recommended in both groups (calories; group I 1633+/-417 kcal per day versus group II 1707.5 +/- 579 kcal per day:ns) and (fats; group I 73.4 +/- 22.7 g per day versus group II [72.6 +/- 28 g per day:ns), without differences in fatty acid intake profile. Total fiber intake did not reach that recommended in both diets but it was higher in group II ( 9.06 +/- 2.7 g per day versus 25.95 +/- 7.12 g per day: P < 0.05). Soluble fiber intake did not reach that recommended in both diets but it was higher in group II (1.7 +/- 0.58 g per day versus 3.5 +/- 0.96 g per day: P < 0.05). Body weight did not change in both groups during treatment. During treatment, in group II a significant change was detected from baseline in LDL-cholesterol and fasting glucose levels. LDL-cholesterol decreased by 12.8% (P < 0.05) and glucose decreased by 12.3% (P < 0.05). No statistical differences were detected among triglycerides, HDL-cholesterol, and insulin levels. CONCLUSIONS: Modest increases in soluble fiber intake in healthy subjects improved LDL cholesterol and glucose levels.