%0 Journal Article
%T Pharmacokinetics, Tissue Distribution and Excretion of a Novel Diuretic (PU-48) in Rats
%A Bao-Xue Yang
%A Chuang Lu
%A Dan Liu
%A Guo-Liang Zhang
%A Hua Zhang
%A Pu Li
%A Qiang Zhang
%A Xin Wang
%A Ya-Qing Lou
%A Ya-Xin Lou
%A Ying-Yuan Lu
%A Zhi-Yuan Zhang
%J Archive of "Pharmaceutics".
%D 2018
%R 10.3390/pharmaceutics10030124
%X 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¨C¡Þ) 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
%K methyl 3-amino-6-methoxythieno [2
%K 3-b] quinolone-2-carboxylate (PU-48)
%K plasma pharmacokinetics
%K tissue distribution
%K excretion
%K plasma protein binding
%K rat
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160999/