Pharmacokinetic And Pharmacodynamic Interaction Of Terminalia Pallida With Gliclazide In Normal And Diabetic Rats

Abstract

The Current study aims to investigate the interaction between traditionally used anti-diabetic agent hydroalcoholic extract of Terminallia pallida fruits (HATP) and oral hypoglycemic agent gliclazide. Initial dose
optimization was performed after administration of 200 mg/kg and 400 mg/kg of extract and determining
reduction in serum glucose levels in normal rats. A pharmacokinetic interaction study was performed in both
normal and streptozocin induced (55 mg/kg) diabetic rats by administration of gliclazide only or combined
with HATP at 400 mg/kg. Single-dose and repeated dose (28 days) pharmacodynamic and pharmacokinetic
interaction studies were performed in diabetic rats after co-administartion by measuring serum glucose levels
and gliclazide levels respectively. Biphasic pharmacokinetic (serum concentration) and pharmacodynamic(
reduction in serum glucose levels) profile was demonstrated by gliclazide. HATP demonstrated higher and
dose proportionate serum glucose reduction at 400 mg/kg in normal rats. The reduction in serum glucose
levels in normal and diabetic rats was significantly higher in the combined group as compared to only
gliclazide group. Repeated co-administartion showed a higher reduction in serum glucose levels as compared
to single time co-administartion. There was a significant variation observed in pharmacokinetic parameters
with single dose co-administartion in normal, diabetic rats and in repeated dose co-administration in diabetic
rats. HATP showed a significant pharmacodynamic and pharmacokinetic interaction with gliclazide, which
necessitates caution and dose adjustment in co-administration of gliclazide with HATP to avoid severe
hypoglycemia.