Pharmacodynamics and Pharmacokinetics Drug Interactions between ?-Mangostin and Gliclazide: A Pre-Clinical Study
Author(s): Srinivasu Matta and Eswar Kumar Kilari*
Abstract
A study was conducted to investigate the impact of α-Mangostin on the pharmacodynamics and pharmacokinetics of gliclazide, a widely used drug for type II diabetes. The study was performed on normal rats, diabetic rats, and normal rabbits, with the administration of selected doses of gliclazide, α-Mangostin, and their combination. Appropriate washout periods were included between treatments. Blood samples were collected from rats and rabbits at regular intervals through retro-orbital and marginal ear vein punctures, respectively. All blood samples were analyzed for glucose using GOD/POD method, for serum insulin using ELISA method, and for gliclazide using HPLC. The results showed that gliclazide produced significant hypoglycemic and antihyperglycemic responses in normal/ diabetic rats and rabbits. The administration of a selected dose of α-Mangostin alone reduced blood glucose levels and improved the hypoglycemic response produced by gliclazide in combination, both in normal and diabetic rats. Similar effects were observed in normal rabbits, along with an enhancement of serum insulin levels. The pharmacokinetic parameters of gliclazide, such as AUC, AUMC, t1/2, Ke, Vdss clearance, and MRT, were significantly altered in normal rabbits when given in combination with α-Mangostin. This indicated changes in the metabolism and distribution pattern of gliclazide in the presence of α-Mangostin, potentially due to plasma protein displacement and inhibition of the CYP450 2C9 enzyme by α-Mangostin, leading to an increase in the plasma concentration of gliclazide. The study suggests that both single and multiple dose treatments may enhance the activity of gliclazide, and therefore, the therapy with the combination requires adjustment of dosing intervals between treatments.
