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

OBJECTIVES

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.

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 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.

RESULTS

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.

CONCLUSIONS

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