Pharmacokinetics, Tissue Distribution and Excretion of a Novel Diuretic (PU-48) in Rats

Autor: Dan Liu, Zhi-Yuan Zhang, Qiang Zhang, Guo-Liang Zhang, Ying-Yuan Lu, Hua Zhang, Xin Wang, Baoxue Yang, Chuang Lu, Ya-Xin Lou, Pu Li, Ya-Qing Lou
Rok vydání: 2018
Předmět:
Zdroj: Pharmaceutics
Volume 10
Issue 3
Pharmaceutics, Vol 10, Iss 3, p 124 (2018)
ISSN: 1999-4923
Popis: Methyl 3-amino-6-methoxythieno [2,3-b] quinoline-2-carboxylate (PU-48) is a novel diuretic urea transporter inhibitor. The aim of this study is to investigate the profile of plasma pharmacokinetics, tissue distribution, and excretion by oral dosing of PU-48 in rats. Concentrations of PU-48 within biological samples are determined using a validated high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. After oral administration of PU-48 (3, 6, and 12 mg/kg, respectively) in self-nanomicroemulsifying drug delivery system (SNEDDS) formulation, the peak plasma concentrations (Cmax), and the area under the curve (AUC0&ndash
&infin
) were increased by the dose-dependent and linear manner, but the marked different of plasma half-life (t1/2) were not observed. This suggests that the pharmacokinetic profile of PU-48 prototype was first-order elimination kinetic characteristics within the oral three doses range in rat plasma. Moreover, the prototype of PU-48 was rapidly and extensively distributed into thirteen tissues, especially higher concentrations were detected in stomach, intestine, liver, kidney, and bladder. The total accumulative excretion of PU-48 in the urine, feces, and bile was less than 2%. This research is the first report on disposition via oral administration of PU-48 in rats, and it provides important information for further development of PU-48 as a diuretic drug candidate.
Databáze: OpenAIRE
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