(1.3)--文献3生物药剂学与药物动力学.pdf

Adv Ther (2019) 36:1618–1627 /10.1007/s12325-019-00956-z ORIGINAL RESEARCH Absolute Bioavailability of Esaxerenone and Food Effects on its Pharmacokinetics After a Single Oral Dose in Healthy Japanese Subjects: An Open-Label Crossover Study Akifumi Kurata . Hidetoshi Furuie . Tomoko Ishizuka . Takafumi Nakatsu . Takako Shimizu . Manabu Kato . Yasuhiro Nishikawa . Hitoshi Ishizuka Received: February 26, 2019 / Published online: May 22, 2019 The Author(s) 2019 ABSTRACT infusion over 1 h, or in the postprandial state as a single oral dose. Plasma samples were taken Introduction : To investigate the absolute before and during the 96 h after drug adminis- bioavailability of esaxerenone and the effects of tration. Drug concentrations were measured food on its pharmacokinetics (PK) after a single using liquid chromatography-tandem mass oral dose in healthy Japanese subjects. spectrometry. PK parameters were calculated Methods : Twenty-four Japanese males aged using noncompartmental analysis, and safety was assessed. 20–45 years were randomised to six groups (each n = 4) in this single-centre, open-label, Results : After fasting intravenous administra- three-way, three-period crossover study. Esax- tion, total body clearance was 3.69 L h-1 and erenone (5 mg) was administered in the fasting volume of distribution was 92.7 L. The plasma state as a single oral dose, single intravenous concentration–time profile of esaxerenone was similar after fasting and postprandial adminis-