PHARMACOKINETIC DRUG INTERACTIONS OF GLICLAZIDE AND ITOPRIDE IN NORMAL AND DIABETIC RATS Original Article RAMA RAO VUNNAM* 1 , SRIHARSHA S. N. 2 , V. V. RAJESHAM 3 1 Faculty of Pharmacy, Dr. K. N Modi University, Newai, Rajasthan, India, 2 Faculty of Pharmacy, Mahathi College of Pharmacy, Madanapalle, Chittoor-Dist, AP, 3 Received: 30 Jun 2015 Revised and Accepted: 24 Aug 2015 Vijaya College of Pharmacy, Munaganoor (V), Hayathnagar (M), Hyderabad Email: ramarao.vunnam@gmail.com ABSTRACT Objective: The present study was aimed to investigate the safety, reliability of Gliclazide and possible drug interaction with Itopride when they were administered as combination treatment. Methods: Studies were conducted in normal and streptozotocin induced diabetic rats with oral administration of selected doses of gliclazide, itopride and their combination. Blood samples were collected from rats by retro orbital/marginal ear vein puncture at regular intervals of time. All the blood samples were analyzed for pharmacokinetic parameters by HPLC method. Results: There was no significant difference in pharmacokinetic parameters of both Gliclazide alone and combination with itopride in healthy and diabetic rats on day 1 and day 8. Conclusion: Based on the results it can be concluded that the concurrent administration of these two drugs have potential benefit without any drug interactions in the effective management of diabetes and gastroparesis. Keywords: Drug interactions, Gliclazide, Itopride, Pharmacokinetics, Gastroparesis, Diabetes mellitus. INTRODUCTION Diabetes mellitus is a metabolic disease in which there are high blood sugar levels over a prolonged period. Diabetes mellitus is due to the pancreas not producing enough insulin or the cells Normally, the muscles of the stomach, which are controlled by the vagus nerve, contract to break up food and move it through the gastrointestinal (GI) tract. of the body not responding properly to the insulin produced [1]. Gastroparesis is a syndrome characterized by delayed gastric emptying [2], in the absence of mechanical obstruction of the stomach. The cardinal symptoms include postprandial fullness (early satiety), nausea, vomiting and bloating [3]. In one tertiary referral series, diabetes accounted for almost one third of cases of Gastroparesis [4]. Diabetes patients with gastroparesis develop retinopathy, neuropathy, nephropathy, nutritional compromise, impaired glucose control, and a poor quality of life [5]. Diabetes is the most common known cause of gastroparesis. People with diabetes have high levels of blood glucose, also called blood sugar. Over time, high blood glucose levels can damage the vagus nerve. Symptoms attributable to gastroparesis are reported by 5 to 12% of patients with diabetes [6, 7, 8, and 9]. Gliclazide is an oral hypoglycemic (anti-diabetic drug) and is classified as a sulfonylurea. Its classification has been ambiguous, as literature uses it as both a first-generation [10], and second-generation [11] sulfonylurea. Gliclazide was shown to protect human pancreatic beta-cells from hyperglycemia- induced apoptosis [12]. It was also shown to have an antiatherogenic effect (preventing accumulation of fat in arteries) in type 2 diabetes [13]. Itopride is a prokinetic benzamide derivative unlike metoclopramide or domperidone. These drugs inhibit dopamine and have a gastro kinetic effect [14]. Itopride is indicated for the treatment of functional dyspepsia and other gastrointestinal conditions [15]. After oral administration Itopride undergoes rapid and extensive absorption with levels of itopride peaking in the blood plasma after only 35 min. Itopride is primarily eliminated via the kidneys having an elimination half-life To treat the coexisting disease, multidrug therapy is inevitable and there is every possibility for a drug interaction to occur when drugs are concomitantly used [17]. of approximately 6 h [16]. MATERIALS AND METHODS Materials Drugs and chemicals Gliclazide and Itopride Methods were procured from Matrix laboratories as a gift sample. Streptozotocin (STZ) was purchased from Sigma Chemical Co. The glucose estimation (GOD-POD) kit (Excel diagnostic, Hyderabad) was procured from the drug store. All HPLC grade solvents (methanol and water) were procured from Finar chemicals Ltd., Ahmadabad. All chemicals used were analytical grade. Animal study Twenty four healthy Wistar rats were (Weighing 200-220 g) selected for this study, all the animals were healthy during the period of the experiment. All efforts were made to maintain the animals under controlled environmental conditions (Temperature 25 °C, Relative Humidity 45% and 12 h alternate lights and dark cycle) with 100 % fresh air exchange in animal rooms, uninterrupted power and water supply. Rats were fed with standard diet and water ad libitum. Induction of experimental diabetes The protocol of animal study was approved by the institutional animal ethics committee (IAEC NO: P16/VCP/IAEC/2012/3/VVR/AE2). Male Wistar rats (200-250 gms) were fasted for 16 h before the induction of diabetes with Streptozotocin (STZ), Animals (n=6) were injected intra peritoneal with 0.22-0.25 ml of freshly prepared solution of STZ (60 mg/ml in 0.01 m citrate buffer, pH 4.5) at a final dose of 60 mg/kg body wt. The diabetic state was assessed in STZ- treated rats by measuring the non-fasting serum glucose concentration after 48 h. Only rats with serum glucose levels greater than 300 mg/dl were selected and used in this experiment. Study design [18] The rats were grouped as follows Group I: Gliclazide (30 mg/kg, oral) alone in single dose/day in diabetic rats up to 8 d. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Issue 10, 2015 Innovare Academic Sciences