Pharmacokinetic and Pharmacodynamic Interaction of 1 Didymocarpus pedicellata with Gliclazide in Normal and 2 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 proportionatehyp oglycemic 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. 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.