American Journal of Drug Delivery and Therapeutics Acesso livre

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Conferência Formulations 2018: A biodisponibilidade relativa de duas formulações farmacêuticas contendo triclabendazol em ovelhas saudáveis ​​​​- Universidade de Medicina e Farmácia Ana Maria Ghelidiu-Iuliu Hatieganu

Ana Maria Ghelidiu

Introdução:

Foi realizada uma investigação para avaliar a farmacocinética do sulfóxido de triclabendazol. O metabolito activo do triclabendazol é o 6-cloro-5-(2,3-diclorofenoxi)-2-metiltio-benzimidazol e avaliar a bioequivalência de dois planos de suspensão oral contendo triclabendazol 50 mg/ml cada em 36 ovinos sãos. Triclabendazol, de marca Egaten, utilizado no tratamento da fasciolíase e paragonimíase. É extremamente viável para ambas as condições. É um indivíduo do grupo dos anti-helmínticos benzimidazol. Os fármacos benzimidazol partilham uma estrutura atómica típica, sendo o triclabendazol a exceção por ter um anel benzénico clorado, mas sem concentração de carbamato. Os benzimidazóis, por exemplo, o triclabendazol, são comummente reconhecidos por se ligarem à beta-tubulina, evitando assim a polimerização dos microtúbulos.

Método:

Para determinar a biodisponibilidade global do produto de ensaio em relação ao item de referência, a investigação foi planeada como um exame híbrido e randomizado, com organização de uma porção solitária, em jejum em cada um dos dois períodos de investigação. Para a garantia das fixações de plasma de ovinos com sulfóxido de triclabendazol, foi criada e aprovada uma técnica rápida e específica de cromatografia fluida superior combinada com espectrometria de massa (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:

Foram determinados os parâmetros farmacocinéticos relevantes como Cmax, AUClast, AUCtot. Os valores médios para o Cmax foram de 56,0 (17,1) µg/ml para o teste e 54,4 (20,1) µg/ml para o produto de referência. Os valores médios da AUCúltima foram de 1655,6 (443,9) µg/ml xh para o medicamento em teste e 1803,3 (750,6) µg/ml xh para o medicamento de referência. Os valores médios para a AUCtot foram de 1702,4 (445,9) µg/ml xh para o teste e 1847,7 (755,6) µg/ml xh para o medicamento de referência, respetivamente. A relação média de bioequivalência entre teste e referência para Cmax e AUClast é de 1,05119 e 0,969058, respetivamente. Os intervalos de confiança a 90% para a proporção das médias do teste de sulfóxido de triclabendazol para referência são de 98,28-112,44% e 87,97-106,75% para Cmax e AUClast, respetivamente, o que está dentro dos gama de bioequivalência convencional de 80-125%. A diferença entre as médias não é estatisticamente significativa para o Tmax dos produtos teste e de referência (teste de Friedman e Kruskal Wallis).

Conclusão:

Assim sendo, foi fundamentado que o item de teste é bioequivalente ao item de referência no que diz respeito à taxa e grau de farmacocinética do sulfóxido de triclabendazol