アメリカの薬物送達と治療学ジャーナル オープンアクセス

抽象的な

製剤 2018 会議: 健康な羊におけるトリクラベンダゾールを含む 2 つの医薬品製剤の相対的バイオアベイラビリティ - アナ マリア ゲリディウ ユリウ ハティエガヌ医科薬科大学

アナ・マリア・ゲリディウ

導入：

トリクラベンダゾール スルホキシドの薬物動態を評価するための調査が行われました。トリクラベンダゾールの活性代謝物は 6-クロロ-5-(2,3-ジクロロフェノキシ)-2-メチルチオ-ベンズイミダゾールであり、健康な羊 36 匹でそれぞれ 50 mg/ml のトリクラベンダゾールを含む経口懸濁液の 2 つのプランの生物学的同等性を評価しました。トリクラベンダゾールは、Egaten というブランド名で、肝蛭症および肺吸虫症の治療に使用されます。この 2 つの症状に非常に有効です。これは、ベンズイミダゾール駆虫薬グループの 1 つです。ベンズイミダゾール薬は一般的な原子構造を共有していますが、トリクラベンダゾールは塩素化ベンゼン環を持ちますが、カルバメート結合を持たないという点で例外です。トリクラベンダゾールなどのベンズイミダゾールは、β-チューブリンに結合して微小管の重合を防ぐことが一般的に知られています。

方法：

試験品と参照品の全体的なバイオアベイラビリティを決定するために、2 つの試験期間のそれぞれで絶食状態下での単一試験を組織するランダム化ハイブリッド試験として調査が計画されました。トリクラベンダゾールスルホキシドの羊血漿固定を保証するために、高速で特異的な高性能流体クロマトグラフィーと質量分析法 (LC-MS/MS) 技術が開発され、承認されました。

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:

Cmax、AUClast、AUCtot などの関連する薬物動態パラメータが決定されました。Cmax の平均値は、試験製品で 56.0 (17.1) µg/ml、参照製品で 54.4 (20.1) µg/ml でした。AUClast の平均値は、試験製品で 1655.6 (443.9) µg/ml xh、参照製品で 1803.3 (750.6) µg/ml xh でした。AUCtot の平均値は、試験製品で 1702.4 (445.9) µg/ml xh、参照製品で 1847.7 (755.6) µg/ml xh でした。Cmax と AUClast の試験製品と参照製品の平均生物学的同等性平均比は、それぞれ 1.05119 と 0.969058 です。トリクラベンダゾールスルホキシドの試験と参照の平均値の比率の 90% 信頼区間は、Cmax と AUClast でそれぞれ 98.28 ～ 112.44% と 87.97 ～ 106.75% であり、これは従来の生物学的同等性範囲の 80 ～ 125% 内にあります。試験製品と参照製品の Tmax の平均値の差は統計的に有意ではありません (Friedman および Kruskal Wallis 検定)。

結論：

したがって、試験品は、トリクラベンダゾールスルホキシドの薬物動態の速度と程度に関して、参照品と生物学的に同等であると推論された。