Pharmacodynamic And Pharmacokinetic Interaction Of Didymocarpus Pedicellata With Gliclazide In Normal And Diabetic Rats

Abstract

This study evaluated possible interaction between Ayurvedic anti-urolithiac agent hydroalcoholic extract of Didymocarpus pedicellata (HADP) leaves and gliclazide. Dose optimization performed by measuring serum glucose levels after 200 and 400 mg/kg HADP administration to normal rats. Pharmacokinetic interaction study in normal rats performed by administration of gliclazide alone and combination with HADP (400 mg/kg). Diabetes was induced by administration of streptozotocin (55 mg/kg) and animals were treated with gliclazide, HADP and combination for 28 days. Pharmacokinetic and dynamic interaction were assessed after single (day 1) and repeated dose (day 28) co-administration by determination of serum gliclazide and glucose levels respectively. Gliclazide showed biphasic concentration time data and glucose reduction with maximum reduction at 2 and 8h post administration. HADP showed dose proportionate hypoglycemic effect in normal rats, hence 400 mg/kg was used for further studies. There was significantly higher decrease in percentage reduction of glucose levels in co-administration group as compared to gliclazide only group in normal, diabetic rats after single and repeated administration. Reduction was higher in repeated administration as compared to single. There was a non-significant increase in pharmacokinetic parameters in normal and diabetic rats after single HADP administration. Repeated HADP administration in diabetic rats caused significant increase in all pharmacokinetic parameters of gliclazide. On day 28 biochemical parameters are estimated to evaluate effect on oral administration of HADP with gliclazide for 28 days to diabetic animals. The results are shown a significant improvement in dyslipidemia, triglyceride levels and liver functional parameters such as SGOT, SGPT, ALP, and total protein in HADP combination as compared to the vehicle control group. Combination of gliclazide and HADP showed a significant pharmacodynamic and pharmacokinetic interaction with gliclazide. Hence precautions has to be observed in co-administration of gliclazide with HADP and dosage adjustments of gliclazide might be required in a clinical setting to avoid sever hypoglycemia.