Pharmacokinetic and Pharmacodynamic Interactions Between Concomitantly used Gliclazide with Pravastatin
Abstract
Diabetic hyperlipidemia is associated with increased lipoproteins in the blood hence, the introduction of a lipid lowering drugs aids in controlling the same. This comedication may lead to drug–drug interactions between anti-diabetic and anti-hyperlipidemic drugs. The current research is aimed at evaluating the pharmacodynamic and pharmacokinetic interactions of gliclazide (anti-diabetic) therapy by pravastatin (anti-hyperlipidemic) when administrated in combination. The studies conducted on rats dosed with gliclazide, pravastatin individually and in combination. Statistical comparisons of plasma concentration – response study in groups with gliclazide alone, pravastatin alone and in combination was carried out. The response study among concentrations and time were calculated employing student’s paired T-Test. The results indicate that gliclazide is completely absorbed with peak plasma concentration of 6.82±0.12 ng/ml and 7.82±0.12 ng/ml when administrated alone and 7.22±0.12 ng/ml and 7.22±0.12 ng/ml when administrated in combination in diabetic rats on first day (day 1) and eighth day (day8) respectively. Similarly peak plasma concentration of pravastatin are 3.92±0.03 ng/ml and 4.80±0.04 ng/ml when administrated alone and 3.683±0.02 ng/ml and 4.657±0.04 ng/ml when administrated in combination in diabetic rats on first day (day 1) and eighth day (day 8) respectively.There was no statistically noteworthy variation observed in peak plasma concentration (P>0.05). Similarly no variations observed in values of tmax, AUC and T1/2. The fasting serum glucose concentrations in normal and STZ-induced diabetic group on first day (day 1) and eighth day (day 8) were analyzed. The reduction of blood glucose levels at different time intervals on administration of gliclazide and pravastatin alone and in combination analyzed and results indicate no significant change in pharmacodynamic parameters.
Hence the results conclude that combinational therapy of gliclazide and pravastatin were found safe and highly potential in treating hyperlipidemia patients.
Keywords:
Pravastatin, gliclazide, diabetic hyperlipidemia, pharmacokinetic, pharmacodynamicsDOI
https://doi.org/10.25004/IJPSDR.2020.120612References
Alvim MM, Silva LA, Leite IC, Silvério MS. Adverse events caused by potential drug-drug interactions in an intensive care unit of a teaching hospital. Rev Bras Ter Intensiva. 2015; 27:353–359.
Moura C, Prado N, Acurcio F. Potential drug-drug interaction associated with prolonged staysin the intensive care unit: a retrospective cohort study. Clin Drug Investig. 2011; 31:309–316.
Bussing R, Gende A. Severe hypoglycemia from clarithromycin-sulfonylurea drug interaction. Diabetes Care 2002; 25(9): 1659–1661.
Gribble FM, Tucker SJ, Seino S, Ashcroft FM. Tissue specificity of sulfonylureas studies on cloned cardiac and βcell KATP channels. Diabetes 1998;47(9): 1412–1418.
Harrower D. Efficacy of gliclazide in comparison with other sulphonylureas in the treatment of NIDDM. Diabetes Res Clin Pract. 1991; 14(2): S65– S67.
Ziegler O, Drouin P. Hemobiological properties of gliclazide. J Diabetes Complications. 1994; 8(4): 235–239.
Pan HY, DeVault AR, Swites BJ. Pharmacokinet ics and pharmacodynamics of pravastatin alone and with cholestyramine in hypercholesterolemia. Clin Pharmacol and Therap. 1990; 48(2): 201–207.
Hsu, Spinler SA, Johnson NE. Comparative evaluation of the safety and efficacy of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. Ann Pharmacother. 1995; 29(7-8):743–759.
Hatanaka T. Clinical pharmacokinetics of Pravastatin mechanisms of pharmacokinetic events. Clin Pharmacokinet. 2000; 39(6): 397–412.
Jacobsen W, Kirchner G, Hallensleben K. Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Drug Metab Dispos. 1999; 27(2): 173–179.
Transon C, LeemannT, Dayer P. In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol. 1996; 50 (3): 209–215.
Nagy CF. Concurrent administration of donepezil HCl and sertraline HCl in healthy volunteers: assessment of pharmacokinetic changes and safety following single and multiple oral doses. Br J Clin Pharmacol. 2004; 58: 25-33.
Davit BM. Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration. Ann Pharmacother. 2009; 43: 1583-1597.
Meredith P. Bioequivalence and other unresolved issues in generic drug substitution. Clin Ther. 2003; 25: 2875-2890.
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