POTASYUM 2-((4-AMİNO-5-(MORFOLİNOMETİL)-4H-1,2,4-TRİAZOL-3-İL)TİYO) ASETATIN FARMAKOKİNETİĞİ VE POTANSİYEL METABOLİTLERİNİN SIÇANLARDA ARAŞTIRILMASI

Abstract

Amaç: Bu çalışmanın amacı, sıçanlara intragastrik olarak uygulanan potasyum 2-((4-amino-5-(morfolinometil)-4H-1,2,4-triazol-3-il)tiyo) asetat maddesinin, belirli farmakokinetik parametrelerini ve olası metabolitlerini incelemektir.

Gereç ve Yöntem: Çalışma Wistar sıçanları üzerinde gerçekleştirilmiştir ve farmakokinetik özellikleri değerlendirmek için aşağıdaki parametreler hesaplanmıştır: Farmakokinetik eğri altındaki alan (AUC), toplam klerens (CL), eliminasyon sabiti (K), toplam dağılım hacmi (VT) ve serum yarılanma ömrü (t1/2). Ayırım, Agilent 1260 Infinity HPLC sistemi kullanılarak gerçekleştirilmiştir.

Sonuç ve Tartışma: Kan serumundaki potasyum 2-((4-amino-5-(morfolinometil)-4H-1,2,4-triazol-3-il)tiyo) asetat konsantrasyonunun belirlenmesi, 0.08 (5 dakika), 0.25 (15 dakika), 0.75 (45 dakika), 2.5, 7.5, 13.5 ve 24 saat boyunca gerçekleştirilmiştir. Sıçanların kan serumunda, enjekte edilen maddenin maksimum konsantrasyonuna, uygulamadan hemen sonra, ortalama 279.67 μg/ml'lik bir değerle ve 5 dakika içinde ulaşıldığı bulunmuştur. Bu aşamadan sonra, konsantrasyon mono-exponential olarak azalmıştır ve bu durum dağılım ve eliminasyonun aynı oranda devam ettiğini göstermiştir. Farmakokinetik eğri altındaki alan (AUC) = 150.8998 μg*h/ml olup, belirtilen maddenin serum yarılanma ömrü belirlenmiştir (t1/2 = 0,32 saat). Elde edilen kromatogramlara ve kütle spektrumlarına dayanarak, sıçanlara intragastrik uygulama sonucunda, 5 adet olası potasyum 2-((4-amino-5-(morfolinometil)-4H-1,2,4-triazol-3-il)tiyo) asetat metaboliti belirlenmiştir.

Keywords

• 1.2.4-triazol
• farmakokinetik
• metabolitler

AN INVESTIGATION OF THE PHARMACOKINETICS AND POTENTIAL METABOLITES OF POTASSIUM 2-((4-AMINO-5- (MORFOLINOMETYL)-4H-1,2,4-TRIAZOL-3-YL)THIO) ACETATE ON RATS

Abstract

Objective: The purpose of this work is to study the designated pharmacokinetic parameters and possible metabolites of the substance potassium 2-((4-amino-5-(morfolinometyl)-4H-1,2,4-triazol-3-yl)thio)acetate by intragastric introduction to rats.

Material and Method: The study was performed on Wistar rats. The following parameters were calculated to evaluate the pharmacokinetic properties: area under the pharmacokinetic curve (AUC), apparent clearance (CL), elimination rate constant (K), volume of distribution (VT), serum half-life (t1⁄2). Separation was performed using Agilent 1260 Infinity HPLC system.

Result and Discussion: The determination of the concentration of potassium 2-((4-amino-5-(morfolinometyl)-4H-1,2,4-triazol-3-yl)thio)acetate in serum was performed for 0.08 (5 min), 0.25 (15 min), 0.75 (45 min), 2.5, 7.5, 13.5 and 24 hours. It was found that in the serum of rats the maximum concentration of the injected substance was reached almost immediately after administration, namely for 5 min with an average value at the level of 279,67 µg/ml. Thereafter, the concentration decreases mono-exponential, which indicates that the distribution and elimination occur at the same rate. The area under the pharmacokinetic curve is AUC = 150,8998 µg*h/ml. The serum half-life of the specified substance is established (t1⁄2 = 0.32 hours). Based on the obtained chromatograms and mass spectra, 5 possible metabolites of potassium 2-((4-amino-5-(morfolinometyl)-4H-1,2,4-triazol-3-yl)thio)acetate (PKR-173)were determined by intragastric introduction to rats.

Keywords

• 1.2.4-triazole
• metabolite
• pharmacokinetics

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