Yamamoto Yutaro, Yamamoto Yuta, Saita Tetsuya, Hira Daisuke, Chijiwa Takahito, Shin Masashi
Department of Applied Life Science, Faculty of Biotechnology and Life Science, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
Acta Histochem Cytochem. 2020 Jun 26;53(3):55-60. doi: 10.1267/ahc.19036. Epub 2020 May 29.
Alogliptin is one of a new class of therapeutic agents for type 2 diabetes called dipeptidyl peptidase-4 inhibitors. Here, we used immunohistochemistry to investigate the pharmacokinetics of alogliptin at the cell and tissue levels in the rat kidney and liver. One hour after alogliptin administration, the most noticeable immunoreactivity in the kidney was a moderate-to-strong staining in proximal tubule S3 segment epithelial cells. On the other hand, immunostaining was found only in the microvilli of S1 and S2 segment cells. Immunoreactivity was also observed in the glomerulus and distal tubules. Positive cells and almost negative cells coexisted in the collecting ducts. Twenty-four hours after administration, moderate immunostaining remained in the S3 segment but staining in other regions had almost disappeared. In the liver 1 hr after administration, hepatocyte staining differed in the hepatic lobule, with zone III being stronger than zone I. Immunostaining had almost disappeared 24 hr after administration. These findings suggest that alogliptin reabsorption at the kidney and uptake at the hepatocyte vary from region to region and that one or more types of transporter are involved in these processes. In addition, long-term alogliptin use may cause the drug to accumulate in S3 segment, leading to adverse events.
阿格列汀是一类新型的2型糖尿病治疗药物——二肽基肽酶-4抑制剂中的一种。在此，我们采用免疫组化方法，在大鼠肾脏和肝脏的细胞及组织水平上研究阿格列汀的药代动力学。给予阿格列汀1小时后，肾脏中最明显的免疫反应性是近端小管S3段上皮细胞出现中度至强染色。另一方面，仅在S1和S2段细胞的微绒毛中发现免疫染色。在肾小球和远端小管中也观察到免疫反应性。集合管中存在阳性细胞和几乎阴性的细胞。给药24小时后，S3段仍保留中度免疫染色，但其他区域的染色几乎消失。给药1小时后，肝脏中肝细胞染色在肝小叶中有所不同，Ⅲ区比Ⅰ区更强。给药24小时后免疫染色几乎消失。这些发现表明，阿格列汀在肾脏的重吸收和在肝细胞的摄取因区域而异，并且这些过程涉及一种或多种类型的转运体。此外，长期使用阿格列汀可能导致药物在S3段蓄积，从而引发不良事件。
