Abstract

PHARMACODYNAMIC HERB-DRUG INTERACTIONS: THE EFFECTS OF AZADIRACHTA INDICA LEAF EXTRACTS ON TWO COMMONLY USED SECOND GENERATION SULFONYLUREAS

Sunday Odunke Nduka, Ajaghaku Lotanna Daniel*, Emmanuel Emeka Ilodigwe, Uju Adimorah, Sonnie Ikechukwu Mbagwu

ABSTRACT

The co-administration of A. indica – an herb with reported hypoglycermic effect, with antidiabetic drugs is a common practice with little or no concern of possible herb-drug interactions that may affect patients’ treatment outcomes. We Evaluated herb-drug interactions between A. indica and two second generation sulfonylureas- glibenclamide and glimepiride in streptozotocin induced diabetic animal model. Both immediate drug-extract interactions and 10 days administration of aqueous extract of A. indica prior to co-administration with the drugs were assessed. Diabetes was induced on the animals intraperitoneally using 70 mg/kg streptozotocin. Animals with fasting blood glucose > 160 mg/dl were considered diabetic and grouped for the study. The extract, glibenclamide and glimepiride produced progressive significant (p < 0.05) reductions in blood glucose when administered alone. Co-administration of the extract with glibenclamide produced antagonistic herb-drug interactions that started from 0.5 h of co-administration. Higher antagonistic interactions were recorded with 10 days pre-treatment with the extract prior the administration of the agents. Antagonistic interaction was also reproduced with the extract and glimepiride co-administration similar to that of glibenclamide. Result from this study established for the first time negative interactions between A. indica leave extract and the agents- glibenclamide and glimepiride and as such provides scientific evidence to guide patients and health care providers. However, further investigation is required to elucidate possible mechanism(s) of interaction.

Keywords: Antagonism; Azadirachta indica ; Glibenclamide; Glimepiride; Herb-drug interactions.