School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
Hanmi Research Center, Hanmi Pharm. Co. Ltd., Gyeonggi-do, Republic of Korea.
In Vivo. 2021 Nov-Dec;35(6):3245-3251. doi: 10.21873/invivo.12619.
BACKGROUND/AIM: Using a rat model of collagen-induced arthritis (CIA), we evaluated the therapeutic effects of HM71224 (BTKi), as well as the drug-drug interactions in combined therapy with methotrexate (MTX) based on both drugs' pharmacological role in immune regulation and antiinflammation.
Arthritis in rats was induced using type II collagen and incomplete Freund's adjuvant. The therapeutic effects of HM71224 (alone or in combination with MTX) were evaluated by arthritis score, paw volume, body weight, and histopathological examination (H&E and Safranin-O staining). The drug-drug interactions between HM71224 and MTX were investigated by measuring plasma, liver enzyme and creatinine levels and blood cell counts.
HM71224 reduced the clinical signs of arthritis, paw volume, and body weight loss in CIA rats. ED and ED were 1.0 and 2.5 mg/kg, respectively. HM71224 combined with MTX decreased the arthritis score, bone erosion, synovitis, and cartilage degradation without apparent interaction.
The combination of HM71224 and MTX improved the therapeutic effect with no drug-drug interactions in RA.
背景/目的：我们使用胶原诱导性关节炎（CIA）大鼠模型，评估了 HM71224（BTKi）的治疗效果，以及在免疫调节和抗炎方面基于两种药物的药理学作用与甲氨蝶呤（MTX）联合治疗时的药物相互作用。
使用 II 型胶原和不完全弗氏佐剂诱导大鼠关节炎。通过关节炎评分、爪体积、体重和组织病理学检查（H&E 和番红 O 染色）评估 HM71224（单独或与 MTX 联合）的治疗效果。通过测量血浆、肝酶和肌酐水平以及血细胞计数来研究 HM71224 和 MTX 之间的药物相互作用。
HM71224 减轻 CIA 大鼠的关节炎临床症状、爪体积和体重减轻。ED 和 ED 分别为 1.0 和 2.5mg/kg。HM71224 与 MTX 联合使用可降低关节炎评分、骨侵蚀、滑膜炎和软骨降解，而无明显的相互作用。
HM71224 与 MTX 的联合使用改善了 RA 的治疗效果，无药物相互作用。
