Akowuah Gabriel Akyirem, Sabbagh Bassel Al, Palanirajan Vijayaraj Kumar, Chew Yik-Ling, Chin Jin Han, Ahmad Mariam
School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Subang, Malaysia.
Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia.
J Complement Integr Med. 2024 Dec 24;22(1):134-141. doi: 10.1515/jcim-2024-0217. eCollection 2025 Mar 1.
Del. leaves are used in traditional Southeast Asia and Africa medicinal practices. Metformin is used for diabetes management. This study investigated the effect of a single dose of aqueous leaf extract of on metformin pharmacokinetics in diabetic rats.
Diabetic rats were randomly assigned to four groups, with six rats in each group. Group 1 was administered distilled water. Group 2 was administered aqueous leaf extract alone. Group 3 was administered metformin alone. Group 4 was co-administered extract plus metformin. Blood was collected at predetermined intervals, and plasma metformin levels were measured with liquid chromatography. The area under the curve (AUC), maximum plasma concentration (C), time to reach C (T), half-life (t), and clearance (CL), were calculated based on noncompartment analysis. The effect of the extract on CYP2C9, CYP3A4, and UGT activities was determined using a Fluorometric Screening Kit.
The combined treatment altered the pharmacokinetic parameters of metformin. The T increased from 90±0.18 min to 180±0.13 min and the C increased from 0.91±0.32 μg/mL to 2.153±0.28 μg/mL. Additionally, the AUC increased from 118.25±1.37 μg min mL to 301.006±1.96 μg min mL and the t increased from 34.69±0.61 min to 101.321±0.55 min. However, the CL rate was decreased. The extract inhibited CYP3A4 and CYP2C9 enzyme activities.
The alteration of pharmacokinetic parameters by the extract suggests potential herb-drug interactions.
在东南亚和非洲的传统医学实践中使用德尔叶。二甲双胍用于糖尿病管理。本研究调查了单剂量德尔叶水提取物对糖尿病大鼠二甲双胍药代动力学的影响。
将糖尿病大鼠随机分为四组，每组六只。第1组给予蒸馏水。第2组单独给予德尔叶水提取物。第3组单独给予二甲双胍。第4组联合给予德尔叶提取物和二甲双胍。在预定时间间隔采集血液，用液相色谱法测量血浆二甲双胍水平。基于非房室分析计算曲线下面积（AUC）、最大血浆浓度（C）、达到C的时间（T）、半衰期（t）和清除率（CL）。使用荧光筛选试剂盒测定提取物对CYP2C9、CYP3A4和UGT活性的影响。
联合治疗改变了二甲双胍的药代动力学参数。T从90±0.18分钟增加到180±0.13分钟，C从0.91±0.32μg/mL增加到2.153±0.28μg/mL。此外，AUC从118.25±1.37μg·min/mL增加到301.006±1.96μg·min/mL，t从34.69±0.61分钟增加到101.321±0.55分钟。然而，CL率降低。提取物抑制CYP3A4和CYP2C9酶活性。
提取物对药代动力学参数的改变提示存在潜在的草药-药物相互作用。
