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Drug-drug Interaction between Pravastatin and Gemfibrozil (Antihyperlipidemic) with Gliclazide (Antidiabetic) in Rats.

Sultanpur C, Satyanarayana S, Reddy N, Kumar K, Kumar S - J Young Pharm (2010)

Bottom Line: Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels.All the blood samples were analyzed for glucose by GOD -POD.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.

View Article: PubMed Central - PubMed

Affiliation: Pharmacology Division, Government College of Pharmacy, Bangalore - 560 027, India.

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.

No MeSH data available.


Related in: MedlinePlus

The mean percent blood glucose change with gliclazide alone and gliclazide + pravastatin + gemfibrozil combination in normal rats (n = 6)
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Figure 0001: The mean percent blood glucose change with gliclazide alone and gliclazide + pravastatin + gemfibrozil combination in normal rats (n = 6)

Mentions: Gliclazide produced biphasic hypoglycaemic activity, with maximum reduction of 38.51 ± 1.65% and 37.29 ± 3.48% at 2 and 8 h in normal rats [Table 1, Figure 1], and hypoglycemic activity with maximum reduction of 37.61 ± 0.38% and 38.12 ± 1.47% at 2 and 8 h in diabetic rats [Table 2, Figure 2], respectively. Gliclazide, when given in combination with pravastatin and gemfibrozil, produced increased hypoglycemic effect with maximum reduction of 51.44 ± 2.10% and 53.19 ± 1.72% and 57.18 ± 0.81% and 56.27 ± 0.56% in the blood glucose in normal and diabetic rats at 2 and 8 h, respectively.


Drug-drug Interaction between Pravastatin and Gemfibrozil (Antihyperlipidemic) with Gliclazide (Antidiabetic) in Rats.

Sultanpur C, Satyanarayana S, Reddy N, Kumar K, Kumar S - J Young Pharm (2010)

The mean percent blood glucose change with gliclazide alone and gliclazide + pravastatin + gemfibrozil combination in normal rats (n = 6)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3021690&req=5

Figure 0001: The mean percent blood glucose change with gliclazide alone and gliclazide + pravastatin + gemfibrozil combination in normal rats (n = 6)
Mentions: Gliclazide produced biphasic hypoglycaemic activity, with maximum reduction of 38.51 ± 1.65% and 37.29 ± 3.48% at 2 and 8 h in normal rats [Table 1, Figure 1], and hypoglycemic activity with maximum reduction of 37.61 ± 0.38% and 38.12 ± 1.47% at 2 and 8 h in diabetic rats [Table 2, Figure 2], respectively. Gliclazide, when given in combination with pravastatin and gemfibrozil, produced increased hypoglycemic effect with maximum reduction of 51.44 ± 2.10% and 53.19 ± 1.72% and 57.18 ± 0.81% and 56.27 ± 0.56% in the blood glucose in normal and diabetic rats at 2 and 8 h, respectively.

Bottom Line: Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels.All the blood samples were analyzed for glucose by GOD -POD.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.

View Article: PubMed Central - PubMed

Affiliation: Pharmacology Division, Government College of Pharmacy, Bangalore - 560 027, India.

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.

No MeSH data available.


Related in: MedlinePlus