Preclinical Pharmacokinetic Studies of a Novel Diuretic Inhibiting Urea Transporters.

ABSTRACT: Urea transporter (UT) inhibitors are a class of promising novel diuretics that do not cause the imbalance of Na⁺, K⁺, Cl^-, and other electrolytes. In our previous studies, 25a, a promising diuretic candidate inhibiting UT, was discovered and showed potent diuretic activities in rodents. Here, a sensitive liquid chromatography-tandem mass spectrometry method for the quantitation of 25a in rat plasma, urine, feces, bile, and tissue homogenates was developed and validated to support the preclinical pharmacokinetic studies. The tissue distribution, excretion, and plasma protein binding were investigated in rats. After a single oral dose of 25a at 25, 50, and 100 mg/kg, the drug exposure increased linearly with the dose. The drug accumulatio

SUBMITTER: Xu Y 

PROVIDER: S-EPMC9027532 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature