Abstract

1. Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.

2. The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.

3. The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.

4. The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.

摘要

1. 糖尿病是一种慢性代谢性疾病，具有多种并发症，由于芸香碱的心血管保护和降血脂作用，服用二甲双胍的患者可能会同时服用含有芸香碱的草药。二甲双胍和芸香碱之间可能存在药物相互作用。本研究旨在探讨芸香碱对糖尿病大鼠二甲双胍药效学和药代动力学的影响。

2. 用高脂饮食和低剂量链脲佐菌素诱导糖尿病大鼠模型。含或不含芸香碱的二甲双胍通过口服管饲给药 42 天。评价药效学和药代动力学参数。

3. 药效学结果显示，与单独使用二甲双胍相比，芸香果芸香碱与二甲双胍共同给药可显着降低糖尿病大鼠的血清葡萄糖和脂质谱。药代动力学结果表明，芸香碱与二甲双胍合用不影响二甲双胍的全身暴露和肾脏分布，但增加了肝脏中二甲双胍的浓度。此外，芸香碱通过上调肝脏中的 Oct1 表达增加了 Oct1 介导的二甲双胍摄取到肝细胞中。

4. 上述数据表明，芸香芸香碱增强了二甲双胍的抗糖尿病作用，这可能与芸香芸香碱通过上调 Oct1 增加二甲双胍的肝脏分布有关。