Process Capability Indexes Determination on Tabletting Performance during the Process Validation for Metamizol Tablets

The aim of the present study was to provide a numerical measure, through the process capability indexes (PCIs), C(p) and C(pk), on whether or not the manufacturing process can be considered capable of producing metamizol (500 mg) tablets. They were also used as statistical tool in order to prove the consistency of the tabletting process, making sure that the tablet weight and the content uniformity of metamizol are able to comply with the preset requirements. Besides that, the ANOVA, the t-test and the test for equal variances were applied to this study, allowing additional knowledge of the tabletting phase. Therefore, the proposed statistical approach intended to assure more safety, precision and accuracy on the process validation analysis.

The use of different doses of metamizol for post-operative analgesia in dogs

Objective To evaluate the post-operative analgesic effect of metamizol (dipyrone) administered intravenously at three different doses (15 mg kg(-1), 25 mg kg(-1) and 35 mg kg(-1)) compared to placebo in dogs undergoing ovariohysterectomy. Study design Prospective, comparative, randomized. blinded trial. Animals Forty healthy bitches, aged 1-6 years, weighing 10-35 kg Methods The animals were randomly divided into four groups and received their respective treatments immediately after surgery: placebo group (0.9% saline solution), D15 group (metamizol 15 mg kg(-1) IV), D25 group (metamizol 25 mg kg(-1) IV), D35 group (metamizol 35 mg kg(-1) IV). The following variables were measured: sedation, pulse rate (PR). respiratory rate (f(R)). arterial blood pressure (ABP), plasma catecholamines. serum cortisol, blood urea nitrogen (BUN) and creatinine metabolites. albumin, alanine aminotransferase (ALT), alkaline phosphatase (ALP). hemogram. platelet counts and level of analgesia which was assessed by visual analog (VAS). descriptive and behavioral scales. Patients were monitored for 48 hours after the administration of the analgesic agent. Rescue analgesia (tramadol, 2 mg kg(-1), intramuscularly) was provided for animals with pain scores >= 4, as determined by the VAS or descriptive scale. Results The D25 and D35 groups showed equivalent post-operative analgesia, as shown by decreased pain scores, according to the three different pain scales, and fewer animals that required rescue analgesia. Significantly lower serum cortisol concentrations were observed in the D25 and D35 groups when compared to the placebo and D15 groups. No hematologic, renal, hepatic or clinical adverse effects were observed during the treatment. Conclusions and clinical relevance Metamizol administered intravenously at 25 or 35 mg kg(-1) can provide adequate post-operative analgesia in bitches undergoing ovariohysterectomy.

The Analgesic Effect Of Dipyrone In Peripheral Tissue Involves Two Different Mechanisms: Neuronal K(atp) Channel Opening And Cb(1) Receptor Activation.

Dipyrone (metamizole) is an analgesic pro-drug used to control moderate pain. It is metabolized in two major bioactive metabolites: 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA). The aim of this study was to investigate the participation of peripheral CB1 and CB2 cannabinoid receptors activation in the anti-hyperalgesic effect of dipyrone, 4-MAA or 4-AA. PGE2 (100ng/50µL/paw) was locally administered in the hindpaw of male Wistar rats, and the mechanical nociceptive threshold was quantified by electronic von Frey test, before and 3h after its injection. Dipyrone, 4-MAA or 4-AA was administered 30min before the von Frey test. The selective CB1 receptor antagonist AM251, CB2 receptor antagonist AM630, cGMP inhibitor ODQ or KATP channel blocker glibenclamide were administered 30min before dipyrone, 4-MAA or 4-AA. The antisense-ODN against CB1 receptor expression was intrathecally administered once a day during four consecutive days. PGE2-induced mechanical hyperalgesia was inhibited by dipyrone, 4-MAA, and 4-AA in a dose-response manner. AM251 or ODN anti-sense against neuronal CB1 receptor, but not AM630, reversed the anti-hyperalgesic effect mediated by 4-AA, but not by dipyrone or 4-MAA. On the other hand, the anti-hyperalgesic effect of dipyrone or 4-MAA was reversed by glibenclamide or ODQ. These results suggest that the activation of neuronal CB1, but not CB2 receptor, in peripheral tissue is involved in the anti-hyperalgesic effect of 4-aminoantipyrine. In addition, 4-methylaminoantipyrine mediates the anti-hyperalgesic effect by cGMP activation and KATP opening.

Determinação espectrofotométrica de dipirona em produtos farmacêuticos por injeção em fluxo pela geração de íons triiodeto

A flow injection spectrophotometric procedure was developed for the determination of metamizol in pharmaceutical formulations. The system is based on the reaction between metamizol and triiodide generated in the system by mixing iodate and iodide-starch solutions. The absorbance of triiodide-starch complex giving a steady-state baseline value which was monitored at 580 nm. The inverse peaks caused by metamizol samples were measured and there was a direct relationship between absorbance decreasing and metamizol concentration from 1.4 x 10-4 to 7.0 x 10-4 mol L-1. The RSD was 0.45 % for a metamizol solution 4.2 x 10-4 mol L-1 (n = 10) with a detection limit (three-fold blank standard deviation/slope) of 6.0 x 10-5 mol L-1 The feasibility of the system was demonstrated for the determination of metamizol in commercial samples with sixty results obtained per hour. The results obtained for metamizol in pharmaceutical formulations using the proposed flow procedure and those obtained using an iodimetric procedure are in agreement at the 95% confidence level and within an acceptable range of error.

Determinação turbidimétrica de dipirona em fluxo utilizando um reator contendo cloreto de prata imobilizado em resina poliéster

A simple flow injection procedure was developed for determining dipyrone (1-phenyl-2,3-dimethyl-4-methylaminomethano-5-pyrazolone sodium, metamizol, analgin) in pharmaceutical formulations. The determination is based on the reduction of Ag+ ions to Ag0 by dipyrone. A colloidal suspension of Ag0 produced was transported by carrier solution (0.01 mol L-1 NaOH) and turbidimetrically detected at 425 nm. The analytical curve for dipyrone was linear in the range from 5.0 x 10-4 to 2.5 x 10-3 mol L-1 with a correlation coefficient of 0.9990. The detection limit was 1.3 x 10-4 mol L-1 (3sigmaB/slope). The relative standard deviation for ten successive measurements was 1.8% and an analytical frequency of 45 h-1 was obtained. The recovery values from three samples ranged from 96.0 to 102%.

Intravenous dipyrone for the acute treatment of episodic tension-type headache: A randomized, placebo-controlled, double-blind study

Acute headaches are responsible for a significant percentage of the case load at primary care units and emergency rooms in Brazil. Dipyrone (metamizol) is easily available in these settings, being the most frequently used drug. We conducted a randomized, placebo-controlled, double-blind study to assess the effect of dipyrone in the acute treatment of episodic tension-type headache. Sixty patients were randomized to receive placebo (intravenous injection of 10 ml saline) or 1 g dipyrone in 10 ml saline. We used seven parameters of analgesic evaluation. The patients receiving dipyrone showed a statistically significant improvement (P<0.05) of pain compared to placebo up to 30 min after drug administration. The therapeutic gain was 30% in 30 min and 40% in 60 min. The number of patients needed to be treated for at least one to have benefit was 3.3 in 30 min and 2.2 in 60 min. There were statistically significant reductions in the recurrence (dipyrone = 25%, placebo = 50%) and use of rescue medication (dipyrone = 20%, placebo = 47.6%) for the dipyrone group. Intravenous dipyrone is an effective drug for the relief of pain in tension-type headache and its use is justified in the emergency room setting.

Determinação turbidimétrica de dipirona em fluxo utilizando um reator contendo cloreto de prata imobilizado em resina poliéster

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Síntese e avaliação farmacológica de protótipos candidatos à fármacos para o tratamento dos sintomas da anemia falciforme

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Optimización de un método basado en SPE-LC-MS/MS para la determinación de multiresiduos de compuestos farmacéuticos en aguas depuradas

Universidad de Las Palmas de Gran Canaria, Facultad de Ciencias del Mar, Doctorado en Gestión Costera.

Determinación de contaminantes emergentes en aguas subterráneas del noreste de Gran Canaria

[ES]La presencia de fármacos en el medio natural constituye una creciente preocupación dados los efectos adversos que pueden presentar. Después de ser consumidos y excretados, llegan a las estaciones depuradoras de aguas residuales, en las que pueden no ser eliminados completamente. La reutilización de aguas depuradas para riego puede ser una fuente de contaminación en el agua subterránea, por lo que se ha llevado a cabo un estudio en el acuífero subyacente a un campo de golf regado con aguas depuradas desde 1973 en el NE de Gran Canaria. Las muestras seleccionadas proceden de agua de riego, agua de lixiviado del suelo y aguas subterráneas. Los compuestos determinados fueron atenolol, metamizol, fluoxetina, cafeína, la paraxantina, nicotina y permetrina

Papel del ESAD en el tratamiento del dolor: análisis pre-post intervención en un entorno rural

Objetivos: Determinar la frecuencia de uso de analgésicos en pacientes terminales atendidos en domicilio, analizando factores que pudieran intervenir en la percepción del dolor, además de las actuaciones llevadas a cabo. Material y métodos: Estudio analítico prospectivo e intervencional con pacientes derivados al Equipo de Soporte para Atención Domiciliaria (ESAD) de Barbastro. Variables estudiadas: edad, sexo, número de visitas, tiempo de seguimiento, presencia de dolor y de otros síntomas concomitantes, Escala Visual Analógica (EVA), diagnóstico, analgésicos previos y post-intervención, dosis media previa de analgésicos y post-intervención. Estudio estadístico con SPSS 15.0. Resultados: n = 638, 53,9 % hombres (n = 344), edad media 79,64 ± 10,8 años, 56 % oncológicos (n = 357), seguimiento medio 56 ± 56,56 días, media de 2,68 ± 2,5 visitas por proceso. Dolor en primera visita 43,3 % (n = 276), EVA media 6,54 ± 1,87, dolor 47,1 % de hombres (n = 162) y 38,8 % de mujeres (n = 114) (p < 0,05), dolor en 56,6 % de oncológicos (n = 202) y en 26,3 % de crónico-dependientes (n = 74) (p < 0,001). No diferencias en EVA entre grupos. Entre analgésicos pautados en pacientes con dolor controlado y sin controlar previa intervención del ESAD encontramos diferencias estadísticamente significativas (p < 0,005) en morfina y tramadol, y con mayor significación (p < 0,001) en fentanilo transdérmico y transmucosa, paracetamol, metamizol y AINE, todos más frecuentes en dolor no controlado. Las dosis medias previas de todos estos fármacos no mostraron diferencias significativas entre los grupos, aunque eran mayores en el grupo de dolor no controlado. En estos, se pautan o modifican analgésicos, encontrándose diferencias estadísticamente significativas pre-post intervención (p < 0,001) en fentanilo transdérmico y transmucosa, tramadol, paracetamol, metamizol, AINE, pregabalina y con p < 0,05 en gabapentina. Se obtiene diferencias (p < 0,05) únicamente en las dosis posteriores a la actuación del ESAD en fentanilo transdérmico y codeína. Obtenemos correlaciones positivas entre dolor y anorexia, ansiedad, depresión e insomnio; en pacientes oncológicos entre dolor y ansiedad e insomnio, y en pacientes crónico-dependientes entre dolor, náuseas y depresión. No diferencias entre grupos en uso previo de benzodiacepinas, antidepresivos y otros tratamientos, aunque sí en clínica de depresión, ansiedad e insomnio. Tras intervención, diferencias significativas en uso de estos tratamientos y de sedación. Conclusiones: Tras la actuación del ESAD se puede apreciar el aumento progresivo de todas las medicaciones analgésicas; se debería realizar una valoración completa de la sintomatología del paciente y un tratamiento de síntomas multifactorial, además de interrogar al paciente de forma adecuada acerca de la presencia de síntomas asociados, dada la elevada correlación de los mismos.