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Pharmacokinetic and Pharmacodynamic interaction between Simvastatin and Diltiazem in rats with induced hypercholesterolaemia and hypertension
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 µg/mL to 19.45 ± 0.07 (P < 0.01) and the area under the concentration-time curve (AUC) from 60.19 ± 2.24 µg h/mL to 78.4± 0.80 µg 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.
Synthesis, spectral and crystal studies of 2-(4,6-diamino pyrimidin-2-ylthio)-N-m/p-tolyl/3,4-dimethylacetamides
Heterocyclic molecules always have a demand in medicinal chemistry research. Pyrimidines are interesting and important scaffold for study of biological importance as many essential biomolecules have pyrimidine structure embedded. Pyrimidines are also reported as inhibitors for biological activities like antibacterial, antifungal, anticancer, antiviral, a few to mention. Here we present the synthesis and X-ray crystal structure of the 2-(4,6-diaminopyrimidin-2-ylthio)-N-phenylacetamide derivatives. X-ray diffraction intensity data were collected at room temperature (293K) on a Bruker axs SMART APEXII single crystal X-ray diffractometer equipped with graphite monochromatic Mo Kα (λ=0.71073 Å) radiation and CCD detector. The compound IIIa crystallizes in the monoclinic P21/c space group with four molecules in the unit cell (a=22.857 Å, b=7.4305 Å, c=8.3686 Å, α=90°, β=93.454°, γ=90° and Z=4). The compound IIIb crystallizes in the orthorhombic Pbca space group with eight molecules in the unit cell (a=18.2022 Å, b=7.5132 Å, c=20.0233 Å, α=90°, β=90°, γ=90° and Z=8). The compound IIIc crystallizes in the monoclinic P21/c space group with four molecules in the unit cell (a=24.254 Å, b=7.3424 Å, c=8.4257 Å, α=90°, β=93.282°, γ=90° and Z=4).
RP-HPLC Analytical Method Development and Validation for the Determination of Olmesartan Medoxomil in Bulk Drug and Tablets
A simple, economic, accurate, sensitive and precise reverse phase high performance liquid chromatographic (RP-HPLC) method for the determination of Olmesartan Medoxomil in bulk drug and tablet dosage form was developed and validated as per the ICH Harmonised Tripartite Guideline. The chromatographic separation was carried out on Hypersil GOLD C18 column (150mm × 4.6mm, 5μm ) with acetonitrile and phosphate buffer pH 3 (35:65%) containing 1% of glacial acetic acid at a flow rate of 1.2mL/min and the PDA detection set at 255nm. A linear response was observed over the concentration from 5μg/mL to 25μg/mL (r2 = 0.9999). The recoveries were found to be between 99.47% - 100.35% and the corresponding RSDs between 0.52-0.68. The validation data proved that the assay undergone is sensitive, reproducible and economical and thus can be used for the routine estimation of Olmesartan medoxomil in bulk drug and tablets dosage form.