Abstract
The pharmacokinetic profiles and therapeutic effects of antidiabetic agents may be significantly affected by herb drug interactions. This study lies in its systematic evaluation of the herb drug interaction between Nigella sativa extract and metformin in Alloxan-induced diabetic male rats. Alloxan monohydrate (150mg/kg) was administered intraperitoneally for inducing diabetes. One hundred adult rats were randomly divided into 5 groups each group continue about 20 rats, normogylcimea control, diabetic control, treated with metformin, Nigella sativa and combined oral administration of metformin/Nigella sativa. Metformin plasma concentrations were measured by a validated HPLC/LC–MS method and pharmacokinetic parameters were calculated according to the non-compartmental analysis. The co-treatment of Nigella sativa with metformin considerably elevated the maximum plasma concentration (Cmax) of metformin, and diminished the time to reach Cmax (Tmax) compared to metformin given alone (P≤0.05) suggesting an increase in absorption. Whereas, parameters related to elimination like elimination rate constant, apparent clearance and volume of distribution were not significantly changed. The combination therapy also achieved better glycemic control than either therapy by itself. The results show absorption in chart that Nigella sativa concentration-dependently increases metformin absorption (greater than metabolism/excretion) thus in total leading to significant circumvention of elimination potentials of metformin which highlight the clinical importance of herb drug interactions in diabetes mellitus.

Key words: Alloxan, Antioxidants, Diabetes mellitus, Herb drug, Metformin, Nigella sativa,Pharmacokinetics.