Abstract

1. The metabolism, excretion, and pharmacokinetics of mirogabalin were investigated following a single oral administration of [¹⁴C]mirogabalin at 30 mg/5.55 MBq to six healthy male subjects.

2. The mean recovery values of radioactivity in urine and faeces were 96.85 and 1.21%, respectively. The main component of radioactivity in the plasma, urine, and faeces was mirogabalin. A204-4455 (lactam form), mirogabalin N-glucuronide, and glucuronide of oxidized A204-4455 were detected as minor components in the specimens. Renal clearance of mirogabalin was higher than the glomerular filtration rate of the human kidneys, indicating renal secretion is involved in the clearance.

3. In vitro studies revealed that UDP-glucuronosyltransferase produced two metabolites: A204-4455, formed via mirogabalin acylglucuronide, and a ring-opened form of mirogabalin N-glucuronide.

4. Mirogabalin was absorbed almost completely, and was eliminated via urine. A part of the orally administered dose of mirogabalin was metabolized through glucuronidation at the amine and carboxylic acid moiety, which represents the primary metabolic pathway.

摘要

1. 在六名健康男性受试者单次口服30 mg / 5.55 MBq的[ ¹⁴ C]米格鲁巴林后，研究了米格鲁巴林的代谢，排泄和药代动力学。

2. 尿液和粪便中放射性的平均回收率分别为96.85和1.21％。血浆，尿液和粪便中放射性的主要成分是米洛巴林。在样品中检测到A204-4455（内酰胺形式），米洛巴林N-葡萄糖醛酸和氧化的A204-4455的葡萄糖醛酸作为次要成分。米洛巴林的肾脏清除率高于人肾脏的肾小球滤过率，表明清除率与肾脏分泌有关。

3. 体外研究表明，UDP-葡萄糖醛酸转移酶可产生两种代谢产物：通过米罗巴林酰基葡糖醛酸形成的A204-4455和米罗巴林N-葡萄糖醛酸的开环形式。

4. Mirogabalin几乎被完全吸收，并通过尿液被清除。口服米罗巴林剂量的一部分通过葡萄糖醛酸化作用在胺和羧酸部分代谢，这代表了主要的代谢途径。