Vernonia amygdalina aqueous leaf extract modulates metformin pharmacokinetics, inhibits CYP3A4 and CYP2C9 enzymes in streptozotocin-induced diabetic rats.

Objectives: Vernonia amygdalina 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 V. amygdalina on metformin pharmacokinetics in diabetic rats.

Methods: Diabetic rats were randomly assigned to four groups, with six rats in each group. Group 1 was administered distilled water. Group 2 was administered V. amygdalina aqueous leaf extract alone. Group 3 was administered metformin alone. Group 4 was co-administered V. amygdalina extract plus metformin. Blood was collected at predetermined intervals, and plasma metformin levels were measured with liquid chromatography. The area under the curve (AUC_0-t), maximum plasma concentration (C_max), time to reach C_max (T_max), half-life (t_1/2), 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.

Results: The combined treatment altered the pharmacokinetic parameters of metformin. The T_max increased from 90±0.18 min to 180±0.13 min and the C_max, increased from 0.91±0.32 μg/mL to 2.153±0.28 μg/mL. Additionally, the AUC_(0-t) increased from 118.25±1.37 μg min mL^-1 to 301.006±1.96 μg min mL^-1 and the t_1/2 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.

Conclusions: The alteration of pharmacokinetic parameters by the extract suggests potential herb-drug interactions.