Abstract

USE OF IN VIVO ANIMAL MODELS TO ASSESS THE EFFECT OF GLIPIZIDE ON PHARMACOKINETIC AND ANTICONVULSANT ACTIVITY OF DIVALPROEX SODIUM

Ashik Banstola*, N.C. Nagalkashmi, Shiva Kumar Swomy, Suresh Janadri

ABSTRACT

The study was conducted to find the influence of Glipizide on the pharmacokinetic and anticonvulsant activity of Divalproex Sodium (DS). Both epilepsy and diabetes are managed clinically by administering various drugs for prolonged period of time. Therefore, polypharmacy are key factors, alarming drug-drug interaction. Healthy albino rabbits were used to study the effect of Glipizide (3.73 mg/kg p.o) on pharmacokinetic parameters of DS (25mg/kg p.o) followed by anticonvulsant activity to confirm the results. The experiment consists of two parts i.e administration of Divalproex alone and in combination with Glipizide after seven days treatment of Glipizide in four healthy albino rabbits. Blood samples were collected at 0, 30 min, 1st, 2nd, 4th, 8th and 16th hour from the marginal ear vein puncture of each rabbit. Serum concentrations were analyzed by a validated Ultra Performance Liquid Chromatography (UPLC) method. For pharmacodynamic study, electrically and chemically induced convulsion tests were used. The concentration of serum DS was found significantly increased after the Glipizide treatment at 1st, 4th, 8th and 16th hour for one week but it failed to exhibit the significant changes at 4th hour. The pharmacokinetic parameters like Area Under Curve (AUC), Area Under first order Moment Curve (AUMC), t1/2, Peak Plasma Concentration (Cmax), Mean Residential Time (MRT) and Time of maximum concentration (Tmax) of DS showed changes after Glipizide treatment for one week in healthy albino rabbits. Glipizide treatment for one week exhibited significant increase of duration of hind limb extensor time by maximal electroshock test and delayed onset of clonic convulsion in Pentylenetetrazole induced seizures test. The results revealed that the drug-drug interaction between DS and Glipizide is at distribution and metabolism.

Keywords: Diabetes, divalproex sodium, drug interactions, Glipizide, pharmacokinetic parameters