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.