Choi Hyeon Gyeom, Park So Yeon, Bae Sung Hun, Chang Sun-Young, Kim So Hee
College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499, Republic of Korea.
Department of Biohealth Regulatory Science, Graduate School of Ajou University, Suwon 16499, Republic of Korea.
Biomol Ther (Seoul). 2024 Sep 1;32(5):601-610. doi: 10.4062/biomolther.2024.008. Epub 2024 Aug 2.
Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, is metabolized through hepatic cytochrome P450 (CYP), specifically CYP3A1/2 and CYP2C11. Prolonged administration of rheumatoid arthritis medications is generally associated with an increased risk of renal toxicity. Loganin (LGN), an iridoid glycoside, has hepatorenal regenerative properties. This study investigates the potential of LGN to mitigate acute kidney injury (AKI) and its effects on the pharmacokinetics of tofacitinib in rats with cisplatin-induced AKI. Both intravenous and oral administration of tofacitinib to AKI rats significantly increased the area under the plasma concentration-time curve from time 0 to infinity (AUC) compared with control (CON) rats, an increase attributed to the decelerated non-renal clearance (CL) and renal clearance (CL) of tofacitinib. Administration of LGN to AKI rats, however, protected kidneys from severe impairment, restoring the pharmacokinetic parameters (AUC, CL, and CL) of tofacitinib to those observed in untreated CON rats, with partial recovery of kidney function, as evidenced by an increase in creatinine clearance (CL). Possible interactions between drugs and natural components should be considered, especially when co-administering both a drug and a natural extract containing LGN or iridoid glycosides to patients with kidney injury.
托法替布是一种用于治疗类风湿性关节炎的 Janus 激酶（JAK）抑制剂，通过肝脏细胞色素 P450（CYP）代谢，特别是 CYP3A1/2 和 CYP2C11。类风湿性关节炎药物的长期给药通常与肾毒性风险增加有关。马钱苷（LGN）是一种环烯醚萜苷，具有肝肾再生特性。本研究调查了 LGN 减轻急性肾损伤（AKI）的潜力及其对顺铂诱导的 AKI 大鼠中托法替布药代动力学的影响。与对照（CON）大鼠相比，给 AKI 大鼠静脉内和口服托法替布均显著增加了从时间 0 到无穷大的血浆浓度 - 时间曲线下面积（AUC），这一增加归因于托法替布的非肾清除率（CL）和肾清除率（CL）减慢。然而，给 AKI 大鼠施用 LGN 可保护肾脏免受严重损伤，使托法替布的药代动力学参数（AUC、CL 和 CL）恢复到未治疗的 CON 大鼠中观察到的水平，肾功能部分恢复，这通过肌酐清除率（CL）增加得到证明。应考虑药物与天然成分之间可能的相互作用，特别是当同时给肾损伤患者施用药物和含有 LGN 或环烯醚萜苷的天然提取物时。
