Pharmacokinetics, Tissue Distribution and Excretion of a Novel Diuretic (PU-48) in Rats
AbstractMethyl 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–∞) 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. View Full-Text
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Zhang, Z.-Y.; Zhang, H.; Liu, D.; Lu, Y.-Y.; Wang, X.; Li, P.; Lou, Y.-Q.; Yang, B.-X.; Lou, Y.-X.; Lu, C.; Zhang, Q.; Zhang, G.-L. Pharmacokinetics, Tissue Distribution and Excretion of a Novel Diuretic (PU-48) in Rats. Pharmaceutics 2018, 10, 124.
Zhang Z-Y, Zhang H, Liu D, Lu Y-Y, Wang X, Li P, Lou Y-Q, Yang B-X, Lou Y-X, Lu C, Zhang Q, Zhang G-L. Pharmacokinetics, Tissue Distribution and Excretion of a Novel Diuretic (PU-48) in Rats. Pharmaceutics. 2018; 10(3):124.Chicago/Turabian Style
Zhang, Zhi-Yuan; Zhang, Hua; Liu, Dan; Lu, Ying-Yuan; Wang, Xin; Li, Pu; Lou, Ya-Qing; Yang, Bao-Xue; Lou, Ya-Xin; Lu, Chuang; Zhang, Qiang; Zhang, Guo-Liang. 2018. "Pharmacokinetics, Tissue Distribution and Excretion of a Novel Diuretic (PU-48) in Rats." Pharmaceutics 10, no. 3: 124.
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