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.

阿格列汀是一种新型 2 型糖尿病治疗药物，称为二肽基肽酶 4 抑制剂。在这里，我们使用免疫组织化学研究阿格列汀在大鼠肾脏和肝脏细胞和组织水平的药代动力学。施用阿格列汀一小时后，肾脏中最明显的免疫反应性是近端小管 S3 段上皮细胞中的中度至强染色。另一方面，仅在 S1 和 S2 段细胞的微绒毛中发现免疫染色。在肾小球和远端肾小管中也观察到免疫反应性。集合管内阳性细胞和几乎阴性的细胞共存。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。给药后1小时的肝脏中，肝小叶中的肝细胞染色不同，III区强于I区。给药后24小时免疫染色几乎消失。这些发现表明，阿格列汀在肾脏的重吸收和肝细胞的摄取因区域而异，并且一种或多种类型的转运蛋白参与这些过程。此外，长期使用阿格列汀可能导致药物在S3段蓄积，导致不良事件发生。