Biotransformation of Finerenone, a Novel Nonsteroidal Mineralocorticoid Receptor Antagonist, in Dogs, Rats, and Humans, In Vivo and In Vitro
Biotransformation of Finerenone, a Novel Nonsteroidal Mineralocorticoid Receptor Antagonist, in Dogs, Rats, and Humans, In Vivo and In Vitro
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DOI：
10.1124/dmd.118.083337
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发表时间：
2018-11-01
影响因子：
3.9
通讯作者：
Schwarz, Thomas
中科院分区：
文献类型：
--
作者：
Gerisch, Michael;Heinig, Roland;Schwarz, Thomas
非甾体盐皮质激素受体拮抗剂非那利酮的质量平衡和生物转化进行了研究，在4名健康男性志愿者单次口服10 mg（78 μ Ci）的[C-14]非那利酮后，并与犬和大鼠的研究数据进行了比较。给药放射性的总回收率在人体中为101%，在犬中为94.7%，在大鼠中为95.2%。在人体中，放射性主要经肾脏排泄（80%）;在大鼠中，主要经胆汁/粪便途径排泄（76%）;在犬中，排泄更平衡。在所有种属中，非那利酮通过氧化生物转化广泛代谢，在所有三个种属中，每种代谢产物的排泄物中以少量原型药物为主（人：1%;犬，大鼠：79%）。总之，本研究表明，非那利酮是清除氧化生物转化，主要是通过萘啶衍生物。
Mass balance and biotransformation of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, were investigated in four healthy male volunteers following a single oral administration of 10 mg (78 mu Ci) of [C-14]finerenone and compared with data from studies in dogs and rats. The total recovery of the administered radioactivity was 101% in humans, 94.7% in dogs, and 95.2% in rats. In humans, radioactivity was mainly excreted renally (80%); in rats, it was primarily the biliary/fecal route (76%); and in dogs, excretion was more balanced. Finerenone was extensively metabolized in all species by oxidative biotransformation, with minor amounts of unchanged drug in excreta (humans: 1%; dogs, rats: 79%) of each metabolite predominated in all three species. In summary, the present study demonstrates that finerenone is cleared by oxidative biotransformation, mainly via naphthyridine derivatives.