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Abstracto

Conferencia sobre formulaciones 2018: Biodisponibilidad relativa de dos formulaciones farmacéuticas que contienen triclabendazol en ovejas sanas - Ana Maria Ghelidiu-Iuliu Hatieganu Universidad de Medicina y Farmacia

Ana María Ghelidiu

Introducción:

Se realizó una investigación para evaluar la farmacocinética del sulfóxido de triclabendazol. El metabolito activo del triclabendazol es el 6-cloro-5-(2,3-diclorofenoxi)-2-metiltio-bencimidazol y para estudiar la bioequivalencia de dos planes de suspensión oral que contienen triclabendazol 50 mg/ml cada uno en 36 ovejas sanas. El triclabendazol, que tiene la marca comercial Egaten, se utiliza para tratar la fascioliasis y la paragonimiasis. Es muy eficaz para ambas afecciones. Es un miembro del grupo de antihelmínticos benzimidazoles. Los fármacos benzimidazoles comparten una estructura atómica típica, siendo el triclabendazol la excepción al tener un anillo de benceno clorado pero sin grupo carbamato. Se sabe comúnmente que los benzimidazoles, por ejemplo, el triclabendazol se unen a la beta-tubulina, impidiendo así la polimerización de los microtúbulos.

Método:

Para determinar la biodisponibilidad global del producto de prueba con respecto al producto de referencia, el estudio se planificó como un estudio híbrido aleatorizado, con la organización de una sola muestra, en condiciones de ayuno en cada uno de los dos períodos de estudio. Para la determinación de las fijaciones de plasma de oveja con sulfóxido de triclabendazol se diseñó y aprobó una técnica rápida y específica de cromatografía de fluidos superior combinada con espectrometría de masas (LC-MS/MS).

Fluid chromatography–mass spectrometry (LC-MS) is a scientific science strategy that consolidates the physical division capacities of fluid chromatography (or HPLC) with the mass investigation abilities of mass spectrometry (MS). Coupled chromatography - MS frameworks are famous in substance investigation in light of the fact that the individual abilities of every strategy are improved synergistically. While fluid chromatography isolates blends with numerous parts, mass spectrometry gives auxiliary personality of the individual segments with high sub-atomic particularity and discovery affectability. This couple strategy can be utilized to break down biochemical, natural, and inorganic mixes ordinarily found in complex examples of ecological and organic beginning. LC-MS framework contains an interface that productively moves the isolated parts from the LC section into the MS particle source. The interface is essential in light of the fact that the LC and MS gadgets are in a general sense incongruent.  The versatile stage in a Liquid Chromatography framework is a pressurized fluid, the MS analyzers generally work under high vacuum. In this way, it is beyond the realm of imagination to straightforwardly siphon the eluate from the LC section into the MS source. In general, the interface is a precisely straightforward piece of the LC-MS framework that moves the greatest measure of analyte, expels a critical bit of the versatile stage utilized in LC and jelly the synthetic personality of the chromatography items (synthetically idle). As a necessity, the interface ought not meddle with the ionizing productivity and vacuum states of the MS framework. These days, most broadly applied LC-MS interfaces depend on barometrical weight ionization (API) systems like electrospray ionization (ESI), environmental weight synthetic ionization (APCI), and climatic weight photograph ionization (APPI).These interfaces opened up during the 1990s following a multi decade long innovative work process.

The interface between a fluid stage method (HPLC) with a consistently streaming eluate, and a gas eliminate strategy conveyed in a vacuum was hard for quite a while. The approach of electrospray ionization changed this. As of now, the most widely recognized LC-MS interfaces are electrospray ionization (ESI), environmental weight synthetic ionization (APCI), and barometrical weight photograph ionization (APPI). These are more up to date MS particle sources that encourage the progress from a high weight condition (HPLC) to high vacuum conditions required at the MS analyser. In spite of the fact that these interfaces are depicted independently, they can likewise be economically accessible as double ESI/APCI, ESI/APPI, or APCI/APPI particle sources. Different testimony and drying methods were utilized previously (e.g., moving belts) yet the most widely recognized of these was the disconnected MALDI affidavit. Another methodology still a work in progress called direct-EI LC-MS interface, couples a nano HPLC framework and an electron ionization prepared mass spectrometer.

LC-MS is generally utilized in the field of bioanalysis and is uncommonly engaged with pharmacokinetic investigations of pharmaceuticals. Pharmacokinetic examines are expected to decide how rapidly a medication will be cleared from the body organs and the hepatic blood stream. MS analyzers are valuable in these examinations on account of their shorter investigation time, and higher affectability and particularity contrasted with UV identifiers generally joined to HPLC frameworks. One significant favorable position is the utilization of couple MS-MS, where the indicator might be modified to choose certain particles to section. The deliberate amount is the aggregate of atom sections picked by the administrator. For whatever length of time that there are no obstructions or particle concealment, the LC partition can be very brisk. LC-MS is much of the time utilized in tranquilize advancement since it permits speedy atomic weight affirmation and structure recognizable proof. These highlights accelerate the way toward creating, testing, and approving a disclosure beginning from an immense range of items with potential application. LC-MS applications for medicate advancement are profoundly mechanized techniques utilized for peptide mapping, glycoprotein mapping, lipodomics, normal items dereplication, bioaffinity screening, in vivo sedate screening, metabolic soundness screening, metabolite distinguishing proof, pollution recognizable proof, quantitative bioanalysis, and quality control.

The deliberate plasma groupings of triclabendazole sulfoxide were utilized for the assurance of bioequivalence between the test item concerning the reference item. Non compartmental examination of the pharmacokinetic information of triclabendazole sulphoxide demonstrated likeness between first-request energy of the test and reference item.

Results and Discussion:

Se determinaron los parámetros farmacocinéticos relevantes como Cmax, AUClast, AUCtot. Los valores medios para Cmax fueron 56,0 (17,1) µg/ml para la prueba y 54,4 (20,1) µg/ml para el producto de referencia. Los valores medios para el AUClast fueron 1655,6 (443,9) µg/ml xh para la prueba y 1803,3 (750,6) µg/ml xh para el producto de referencia. Los valores medios para el AUCtot fueron 1702,4 (445,9) µg/ml xh para la prueba y 1847,7 (755,6) µg/ml xh para el producto de referencia, respectivamente. La relación media de bioequivalencia de la prueba con la referencia para Cmax y AUClast es 1,05119 y 0,969058 respectivamente. Los intervalos de confianza del 90% para la relación de las medias de la prueba de sulfóxido de triclabendazol con la de referencia son del 98,28-112,44% y del 87,97-106,75% para Cmax y AUClast, respectivamente, lo que se encuentra dentro del rango de bioequivalencia convencional del 80-125%. La diferencia entre las medias no es estadísticamente significativa para el Tmax de los productos de prueba y de referencia (prueba de Friedman y Kruskal Wallis).

Conclusión:

Por lo tanto, se razonó que el elemento de prueba es bioequivalente al elemento de referencia con respecto a la tasa y el grado de farmacocinética del sulfóxido de triclabendazol.