simvastatin

simvastatin

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  SIMVASTATIN BY PROTTAY DUTTA MPH/10055/20 M.PHARM INPHARMACEUTICAL CHEMISTRY PHARMACEUTICAL PROCESS CHEMISTRY(MPC 204T)
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  INTRODUCTION • Simvastatin isa Hypolipedemic drug belonging to the class of Statins. • It is a Lipid-lowering Agent, and is derived synthetically from Lovastatin (formerly known as Mevinclin) which was isolated from Aspergillus Terreus. • Simvastatin is chemically modified derivative of lovastatin. • It reduces very low density lipoprotein (VLDL), triglycerides (TG) and increases high density lipoprotein cholesterol (HDL-C).
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  • It isused along with exercise, diet, and weight loss to decrease elevated lipid levels. • It is also used to decrease the risk of heart problems in those at high risk. • It is taken by mouth. • They are improvement in Endothelial Function, Decreasing Vascular Inflammation, Inhibiting Smooth muscle Proliferation And Immunomodulation. • In the present study, Anti-inflammatory effect of simvastatin was evaluated and it was compared with diclofenac sodium by using Digital Plethysmometer.
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  • Simvastatin (Zocor)is used to treat hypercholesterolemia. • Half life -2 hrs. • HMG-CoA reductase inhibitor. • Metabolized by : CYP3A4 and carboxyl esterases. • Bioavailability of simvastatin is 5 %.
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  SIDE EFFECTS • Avery small number of people taking simvastatin may have mild memory problems or confusion. • may cause or worsen diabetes. • may rarely cause liver problems. • symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
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  MECHANISM OF ACTION
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  PRODUCTION OF SIMVASTATIN MonacolinJ is manufactured through alkaline hydrolysis of lovastatin, a fungal polyketide produced by Aspergillus terreus. Multistep chemical processes for the conversion of lovastatin to simvastatin are laborious, cost expensive and environmentally unfriendly. A biocatalysis process for monacolin J conversion to simvastatin has been developed. However, direct bioproduction of monacolin J has not yet been achieved. Here, we identified a lovastatin hydrolase from Penicillium chrysogenum, which displays a 232-fold higher catalytic efficiency for the in vitro hydrolysis of lovastatin compared to a previously patented hydrolase, but no activity for simvastatin. Furthermore, we showed that an industrial A. terreus strain heterologously expressing this lovastatin hydrolase can produce monacolin J through single-step fermentation with high efficiency, approximately 95% of the biosynthesized lovastatin was hydrolyzed to monacolin J. Our results demonstrate a simple and green technical route for the production of monacolin J, which makes complete bioproduction of the cholesterol-lowering drug simvastatin feasible and promising.
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  PHARMACOKINETICS PARAMETER • Cmax= Maximum drug concentration • Tmax = The time of the maximum concentration. • AUC= Area under the curve. • Ke = Elimination rate . • t1/2 = The drug half life. t1/2 = ln2/ke
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  REFERENCE • https://www.sciencedirect.com/science/article/abs/pii/S1096717617301180 • rxListthe internet drug index . Zocor. http://www.rxlist.com/zocor-drug.htm. Accessed on 13/10/2013. • https://www.drugs.com/simvastatin.html#side-effects • https://pubmed.ncbi.nlm.nih.gov/12067471/