Abstract
Diabetes mellitus is a condition of increased blood glucose level in the body. Antihyperlipidemic drugs like statins and fibrates are widely used for prophylactic treatment in dyslipideamia and atherosclerosis. Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels. Hence, with oral hypoglycemic drugs, the addition of a lipid-lowering drug is necessary for controlling dislipidemia. In such a situation, there may be chances of drug–drug interactions between antidiabetic and antihyperlipidemic drugs. The present study is planned to evaluate the safety of gliclazide (antidiabetic) in the presence of pravastatin and gemfibrozil (antihyperlpidemic) in rats. Studies in normal and alloxan-induced diabetic rats were conducted with oral doses of gliclazide and their combination with pravastatin and gemfibrozil, with an adequate washout period in between the treatments. Blood samples were collected in rats by retroorbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h. All the blood samples were analyzed for glucose by GOD –POD. Gliclazide (½ TD) produced hypoglycemic activity in normal and diabetic rats, with peak activity at 2 and 8 h. Pravastatin (TD) + gemfibrozil (TD) combination treatment increased the hypoglycemic effect of gliclazide in normal rats or diabetic rats when administered together. The interaction observed due to inhibition of both the enzymes (CYP 450 2C9 and CYP 450 3A4) responsible for the metabolism of gliclazide showed increased half-life, which was seen in the present study. Because concomitant administration of gliclazide with provastatin and gemfibrozil in diabetes is associated with atherosclerosis, it should be contraindicated or used with caution.
Highlights
A study of the mechanisms of drug interactions is of much value in selecting the drug combinations to provide rational therapy
The drug interaction studies assume much importance, especially for drugs that have a narrow margin of safety and where the drugs are used for a prolonged period of time
Diabetes mellitus is one such metabolic disorder that needs treatment for prolonged periods, and maintenance of normal blood glucose level is very important in this condition because both hyperglycaemia and hypoglycaemia are unwanted phenomena
Summary
A study of the mechanisms of drug interactions is of much value in selecting the drug combinations to provide rational therapy. Diabetes mellitus is one such metabolic disorder that needs treatment for prolonged periods, and maintenance of normal blood glucose level is very important in this condition because both hyperglycaemia and hypoglycaemia are unwanted phenomena. Sulfonylureas are the drugs of choice in the treatment of type 2 diabetes.[1] Currently, gliclazide, a second-generation sulfonylurea, is preferred in therapy because of its selective inhibitory activity toward pancreatic K+ATP channels,[2] low incidence of producing severe hypoglycemia[3] and other hemobiological effects.[4] It is well established that sulfonylureas produce insulin secretion and improve tissue utilization of glucose at the cellular level,[5] which was
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
