Pharmacokinetic and Pharmacodynamic interaction between Simvastatin and Diltiazem in rats with induced hypercholesterolaemia and hypertension

Venkateshwarlu Eggadi, Sharvana Bhava B.S, Pavani Sriram, Shiva Kumar Revoori, Umasankar kulandaivelu, suresh Gaddam

Abstract


3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are often prescribed along with antihypertensive agents, including calcium antagonists. Simvastatin is an HMG-CoA reductase inhibitor and Diltiazem which calcium antagonist it is metabolized by the cytochrome P450 (CYP) 3A4. The purpose of this study is to investigate drug interactions between simvastatin and diltiazem. In the present investigation, we studied the pharmacokinetics and dynamics of Simvastatin (SIMVA) alone and in combination with Diltiazem (DILT) in hyperlipidemic and hypertensive rats. The standard cholesterol diet was used to induce hyperlipidemia and 10% fructose solution was used to induce hypertension in Wistar rats. The selected drugs were given for 2 weeks by oral route, simvastatin (2 mg/day), followed by 2 weeks of oral diltiazem (15 mg/day) co-administered with simvastatin (2 mg/day). Combined treatment with simvastatin and diltiazem increased the peak concentration (Cmax) of HMG-CoA reductase inhibitors from 15.64 0.29 g/mL to 19.45 0.07 (P < 0.01) and the area under the concentration-time curve (AUC) from 60.19 2.24 g h/mL to 78.4 0.80 g h/mL (P < 0.01) without affecting the cholesterol-lowering effect of simvastatin. In hyperlipidemic rats, SIMVA caused a marked reduction in the lipid profiles but combination with DILT produced a significant change. In pharmacokinetics, witnessed insignificant change in the combination of SIMVA and DILT when compared with SIMVA alone. From the results synergistic activity of SIMVA with DILT was witnessed.


Keywords


Pharmacokinetic; Pharmacodynamic; Hypertension; Hyperlipidemia; Simvastatin; Diltiazem

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References


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DOI: http://dx.doi.org/10.14805/fda.201512.%25p

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