Archivos Venezolanos de Farmacología y Terapéutica

Evaluation of the comparative bioavailability of a test product containing Calcium Dobesilate 1000 mg, in extended release tablets of Leti Laboratories, S.A.V., once a day, against the reference product Doxium®, containing Calcium Dobesilate 500 mg, in immediate release capsules, of Leti Laboratories, S.A.V., given twice a day, for the same total dose of 1000 mg, in healthy volunteers

Objetivo: Comparar la biodisponibilidad entre dos formulaciones de Dobesilato de Calcio luego de administrar un comprimido de 1000 mg, de liberación prolongada (L.P.) una vez al día vs. Doxium®, cápsulas de 500 mg de liberación inmediata en 2 tomas (una c\12 horas). Métodos: Se realizó un estudio cruzado, de dosis única, en condiciones de ayuno, dos tratamientos, dos periodos, dos secuencias, (2x2) con un periodo de lavado de 14 días, en 14 voluntarios sanos. Los sujetos se asignaron de manera aleatoria, a cada una de las secuencias de administración. Se suministró a los voluntarios una dosis única de Dobesilato de Calcio 1000 mg comprimidos de L.P., o 1 cápsula de Doxium® de 500 mg dos dosis, una c\12 horas, vía oral. Se calcularon los parámetros farmacocinéticos (Cmax, Tmax, ABC0-24 y ABC0-inf) por el método trapezoidal; Software: Excel. Se cuantificó la droga en plasma por cromatografía de líquidos y detección UV/Vis. Se compararon las medias y los IC95% entre 80%-125%, para el cociente de los promedios de Cmax, Tmax, ABC0-t y ABC0-inf. Resultados: Cmax 10.15±1.94 μ/mL vs. 8.96±1.88 μ/mL, Tmax 4.79±0.2 h vs. 4.68±0.36, ABC0-24 92.84±15.96 μ/mL/h vs. 88.74±12.86μ/ mL/h y ABC0-∞ 96.57±16.28μ/mL/h vs. 93.35±15.28μ/mL/h, respectivamente. IC95%: Cmax 103.67%-107.93%, ABC0-24 104.61%-108.75% y ABC0-∞ 103.67%-107.93%. Conclusión: Dobesilato de Calcio LP a una dosis diaria de 1000 mg demostró que se absorbe a una misma velocidad medida por la Cmax y en una cantidad medida por la ABC, similar, por lo que debemos esperar efectos terapéuticos similares.

Objective: To compare the bioavailability of two formulations of Calcium Dobesilate after administration of one tablet of 1000 mg extended release (ER) once daily vs. Doxium®, capsules of 500 mg immediate release in 2 doses (one c\12 hours). Methods: A crossover study, single-dose two treatments, two periods, two sequences, (2x2) with a washout period of 14 days, on 14 healthy volunteers was conducted in fasting conditions. Subjects were randomly assigned to each of the administration sequences. Volunteers received a single dose of 1000 mg Calcium Dobesilate tablets LP, or 1 capsule of 500 mg dose Doxium® every 12 hours orally for 2 doses. Pharmacokinetic parameters were calculated (Cmax, Tmax, AUC0-24 y AUC0-inf) by the trapezoidal method; Software: Excel. The drug was quantified in plasma by liquid chromatography and UV / Vis detection. Comparing the mean and IC95% between 80% -125% for the ratio averages Cmax, Tmax, AUC0-t y AUC0-inf. Results: Cmax 10.15±1.94 μ/mL vs. 8.96±1.88 μ/mL, Tmax 4.79±0.2 h vs. 4.68±0.36 h, AUC0- 24 92.84±15.96 μ/mL/h vs. 88.74±12.86 μ/mL/h and AUC0-∞ 96.57±16.28 μ/mL/h vs. 93.35±15.28 μ/mL/h, respectively. IC95%: Cmax 103.67%-107.93%, AUC0-24 104.61%-108.75% y AUC0-∞ 103.67%-107.93%. Conclusion: Calcium Dobesilate LP at a daily dose of 1000 mg showed to be absorbed at the same speed, as measured by Cmax, and similar quantity, as measured by the AUC, so we expect similar therapeutic effects.

Effectiveness and tolerability of the Petasites hybridus leaf extract Ze 339 in the treatment of allergic rhinitis in a paediatric population

Background: Allergic rhinitis (AR) is one of the most prevalent chronic allergic diseases in children, with a high impact on a childs quality of life and co-morbidities like asthma. Objective: The objective of this analysis was to investigate the effectiveness and tolerability of the Petasites hybridus leaf extract Ze 339 (Ze 339) in the treatment of AR in paediatric patients. Methods: We present a paediatric sub-analysis of a recent Venezuelan observational study, which investigated the effect of Ze 339 on clinical symptoms of AR in patients treated under conditions of daily practice. Among those 927 previously studied patients, 92 patients were less than 18 years old. Thereof, we included 53 children and adolescents in this intention-to-treat sub-analysis. Patients were advised to take one tablet of Ze 339 (corresponding to 8 mg petasins) two or three times a day up to one month. Symptoms of AR were recorded at every medical visit using a 4-point rating scale to indicate the level of severity. Single symptoms of AR (rhinorrhoea, nasal congestion, sneezing, itchy eyes, red eyes, itchy throat) and several composite scores (total symptom score, total nasal symptom score, total nasal and ocular symptom score) were evaluated. The overall therapeutic response of patients to the medication indicating effectiveness and tolerability was evaluated by a 5-point rating scale by both the physician and patient. Results: Full recovery and a significant improvement of symptoms were seen in 86.8% of patients. This was also reflected in a significant improvement of the different composite scores (p<0.001). Overall, the results showed that Ze 339 is effective and well tolerated in the treatment of AR in paediatric patients. Conclusion: Ze 339 is effective and well tolerated in the relief of all symptoms of AR. Beneficial effects were reported by patients and physicians. Ze 339 may be considered for the treatment of AR in paediatric patients.

Nitric oxide as a marker of blunt trauma without intraabdominal damage

Introducción: El Trauma tiene una importante respuesta fisiológica en casi todos los sistemas y órganos. La inducción de la oxido nítrico sintasa debido al trauma por perdidas sanguíneas importantes podría tener resultados devastadores durante estas condiciones pero diversas investigaciones han determinado que existe vasoconstricción y no vasodilatación en estos estados críticos. La razón de esta inhibición es desconocida. Nuestro objetivo es determinar el comportamiento de diferentes mediadores de la respuesta inflamatoria por trauma. El Óxido Nítrico (NO), Malondialdehido (MDA) y la proteína C reactiva. Métodos: Se trata de un estudio prospectivo observacional que se llevo a cabo entre Diciembre del 2008 a Julio del 2009. Se estudiaron 19 pacientes con una edad media de 25,3 ± 2,1 con trauma abdominal sin evidencia clínica de trauma intraabdominal. Los pacientes se abordaron en la Emergencia de Adultos del Hospital Universitario de Maracaibo-Venezuela. Muestras de sangre fueron tomadas inmediatamente a su llegada. Se determinaron ON/MDA y proteína C para luego compararlos con el grupo control sano. Resultados: EL Óxido Nítrico esta significativamente elevado en los pacientes con trauma cuando se compararon con el grupo control(24,7± 5,1 vs 20± 3,3 p:>0,02). No existió cambios en el MDA y PCR en pacientes con trauma cuando se compararon con el grupo control. (1,5± 0,1 vs 1,3± 0,4p: >0,26). Conclusiones: Nuestra investigación demostró que niveles elevados de ON sin aumento del MDA y PCR sugieren la existencia de trauma abdominal sin lesión intraabdominal. La necesidad de aumentar el grupo de estudio que incluya lesión intraabdominal por trauma es un importante paso para determinar el comportamiento de la respuesta inflamatoria en el trauma.

Introduction: Trauma has an important physiologic response in almost every single organ and system.. Nitric oxide sintasa induction do to Trauma and important bleeding could have a devastating consequence however during these conditions research has showed vasoconstriction and not vasodilatation. The reason of this inhibition is unknown. Our goal was to determine the Behavior of important mediators in the inflammatory response do to trauma; Nitric Oxide (NO), Malondialdehyde (MDA) and C Reactive Protein. Methods: This was a prospective observational study undertaken between Janurary 2009 and December 2009. 19 Patients with a mean age mean age of 25,3 ± 2,1 with blunt trauma without clinical evidence of intraabodminal injurie were managed at the Adult emergency trauma area of the University Hospital of Maracaibo-Venezuela. Blood samples were withdrown immediately to their admission. ON/MDA and C reactive protein were determine to later compare results with control healthy group. Results: NO was significally increased in trauma patient when compared with control group (24,7± 5,1 vs 20± 3,3 p:>0,02) No changes were observed in MDA and PCR in Trauma patients when compare with control group(1,5± 0,1 vs 1,3± 0,4p: >0,26). Conclutions: Our research showed that elevated NO with out an increase of MDA and CRP suggest blunt trauma without intraabdominal injurie. The need to have a larger study group that include intraabdominal injury do to blunt trauma is an important step to determine inflammatory behavior in trauma.

Comparative study of the therapeutic efficiency between imiquimod 5% cream and lotion based on polyphenols in the treatment of actinic keratosis

La queratosis actínica se presenta en forma de lesiones premalignas confinadas a la epidermis, producidas por la radiación ultravioleta, que pueden evolucionar a carcinoma de células escamosas el cual es altamente metastásico. Los tratamientos actualmente disponibles comprenden escisión quirúrgica, crioterapia, peeling químico, fototerapia, retinoides, 5-fluoruracilo e imiquimod. Aunque logran tasas de remisión significativas, también es cierto que todos tienen el potencial de provocar efectos colaterales indeseables, que perturban la calidad de vida del paciente y que lo inducen a interrumpir el tratamiento. No hay reportes en la literatura científica del uso de los polifenoles en el tratamiento farmacológico de la queratosis actínica por lo que el objetivo del presente estudio fue comparar la eficiencia terapéutica entre imiquimod al 5% crema y una loción basada en polifenoles en el tratamiento de la queratosis actínica. Para ello se seleccionaron 56 pacientes que fueron asignados de forma aleatoria a uno de los siguientes grupos. Grupo I: recibió dos ciclos de tres semanas de aplicación diaria de Imiquimod crema al 5%, con un intervalo de descanso de 3 semanas, más protector solar diario durante 16 semanas ininterrumpido. Grupo II: recibió loción polifenólica al 5% dos aplicaciones diarias durante 16 semanas más crema protectora solar con polifenoles. Los resultados indican que los polifenoles son tan eficientes como el imiquimod en el tratamiento de la queratosis actínica. El 30% de los pacientes tratados con imiquimod abandonó el tratamiento siendo la razón principal sus efectos adversos, a diferencia del preparado polifenólico que fue bien tolerado por todos los pacientes. En conclusión los polifenoles son una nueva, muy eficiente y segura alternativa para el tratamiento de la queratosis actínica.

Actinic keratosis (AK) presents as premalignant lesions confined to the epidermis, produced by ultraviolet rays, which can evolve to a highly metastatic cancer such as squamous cell carcinoma. Available treatments include surgical excision, criotherapy, chemicals peeling, phototherapy, retinoids, 5-fluoruracil and imiquimod. Even though they achieve significant remission rates, it is also certain that they have the potential to provoke undesirable side effects. There are no reports in previous scientific studies about the use of polyphenols in pharmacological treatment of actinic keratosis. The main objective of this study was to compare the therapeutic efficiency between 5% imiquimod cream and a lotion based on polyphenols in actinic keratosis treatment. For this a total of 56 patients were selected and assigned randomly to one of the following groups. Group I: received two three weeks cycles of a daily application of 5% Imiquimod cream with a 3 week resting period, + a daily application of sun protector during 16 weeks uninterrupted. Group II: received two daily applications of a 5% polyphenolic lotion during 16 weeks. Our results show that the polyphenolic lotion as efficient as imiquimod in the treatment of AK. The 30% of patients treated with imiquimod withdrew from treatment because of undesirable side effects; instead polyphenol treatment was well tolerated by all patients. The polyphenolic preparation was well tolerated by all the patients. In conclusion polyphenols are a new and safe alternative in the treatment of AK.