Methyl 3-amino-6-methoxythieno [2,3-b] quinoline-2-carboxylate (PU-48) is a novel\ndiuretic urea transporter inhibitor. The aim of this study is to investigate the profile of plasma\npharmacokinetics, tissue distribution, and excretion by oral dosing of PU-48 in rats. Concentrations\nof PU-48 within biological samples are determined using a validated high performance liquid\nchromatography-tandem mass spectrometry (LC-MS/MS) method. After oral administration of\nPU-48 (3, 6, and 12 mg/kg, respectively) in self-nanomicroemulsifying drug delivery system\n(SNEDDS) formulation, the peak plasma concentrations (Cmax), and the area under the curve ......... were increased by the dose-dependent and linear manner, but the marked different of\nplasma half-life (t1/2) were not observed. This suggests that the pharmacokinetic profile of PU-48\nprototype was first-order elimination kinetic characteristics within the oral three doses range in rat\nplasma. Moreover, the prototype of PU-48 was rapidly and extensively distributed into thirteen\ntissues, especially higher concentrations were detected in stomach, intestine, liver, kidney, and bladder.\nThe total accumulative excretion of PU-48 in the urine, feces, and bile was less than 2%. This research\nis the first report on disposition via oral administration of PU-48 in rats, and it provides important\ninformation for further development of PU-48 as a diuretic drug candidate.
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