Lovastatin mevacor, marketed by merck under the brand name mevacor, was the first statin class medication ever to come out on the market in the 1980s. The total synthesis of calcium atorvastatin request pdf. All the statin molecules reduce the cholestrol level by same mechanism, where they inhibit the hmgcoa reductase, an important. Lovastatin is indicated as an adjunct to diet for the reduction of elevated total c and ldlc levels in patients with primary hypercholesterolemia types iia and iib 2, when the response to diet restricted in saturated fat and cholesterol and to other nonpharmacological measures alone has been inadequate. Simple organic reactions were used to get to lovastatin as shown in the scheme.
A statin drug, c 24 h 36 o 5, that blocks the bodys. Follow the directions on your prescription label carefully, and. Lovastatin is the first of a new class of cholesterol lowering drugs that competitively inhibit hmgcoa reductase. When used in combination with diet, weight loss, and exercise, lovastatin may reduce the risk of heart attack, stroke, and. Lovastatin is hydrolyzed to the active betahydroxyacid form, which competitively inhibits 3hydroxyl3methylgutarylcoenzyme a reductase, an enzyme involved in cholesterol biosynthesis. Cholesterol is an organic compound, which is produced in humans by a complex metabolism. Mevacor should be used in addition to dietary modifications as part of a treatment plan to lower cholesterol levels when the response to diet and other nonpharmacological measures alone have been inadequate to reduce cardiovascu. Dec 19, 2017 mevacor lovastatin is a cholesterollowering medication called a statin prescribed to treat elevated blood cholesterol levels. Avoid large quantities of grapefruit juice 1 qtday overdose management. Lovastatin is a lactone metabolite isolated from the fungus aspergillus terreus with cholesterollowering and potential antineoplastic activities. Lovastatin mevacor, marketed by merck under the brand name mevacor, was the first statin class medication ever to come out on the. Hirama synthesized compactin and used one of the intermediates to. If used concomitantly, do not exceed lovastatin dosage of 40 mg. Lovastatin mevacor side effects, dosage, interactions.
Lovastatin oral tablet is a statin used to prevent and treat coronary heart disease, and to treat high cholesterol. Mevinolin, monacolin k and mevacor has methyl butyric side chain r 1 and 6a methyl group r 2. Therapeutic class overview statins hmgcoa reductase inhibitors. Lovastatin increased highdensity lipoprotein hdl cholesterol levels 6%. In addition, this agent may induce tumor cell apoptosis and. It is also called as c6 hydroxyl analogue of mevastatin. The pharmacokinetic parameters in 12 hypercholesterolemic subjects at steady state, after 28 days of treatment, comparing altoprev 40 mg to lovastatin immediaterelease 40 mg, are summarized in. Lovastatin biosynthesis by aspergillus terreus in a. Our approach is based on an ugi reaction, which shortens the current synthetic route and is advantageous over the published syntheses. Its available as a generic drug and as the brandname drug altoprev. The synthesis of calcium atorvastatin 1 was performed using the remote 1,5anti asymmetric induction in the boronmediated aldol reaction of. Paralysis of some or all of the muscles of the eye. Take lovastatin at around the same time s every day.
The regular tablet usually is taken once or twice a day with meals. Lovastatin mevacor side effects, dosage, interactions drugs. Lovastatin, sold under the brand name mevacor among others, is a statin medication, to treat. Simvastatin and lovastatin are lipophilic, while pravastatin is hydrophilic. Some of these drug interactions with lovastatin may increase your risk for developing serious muscle problems see mevacor and muscle pain. Feb 24, 2020 lovastatin is used to lower the risk of stroke, heart attack, and other heart complications in people with diabetes, coronary heart disease, or other risk factors. Dietary butter was replaced by egg yolks in hypercholesterolaemic subjects treated with lovastatin mevinolin in order to record the effect of dietary cholesterol loading on serum. Lovastatin belongs to a group of drugs called hmgcoa reductase inhibitors, also known as statins. Inhibits 3hydroxy3methylglutaryl coenzyme a hmg coa reductase, an enzyme which is responsible for catalyzing an early step in the synthesis of cholesterol. Lovastatin mevacor is also one of the less potent of the statin class of medications, but its widely taken and generally well tolerated.
C, apolipoprotein b apo b, and triglycerides tg, and to increase highdensity lipoprotein cholesterol hdlc. Figure 1 shows the synthesis of cholesterol from acetyl coa, and the inhibition. Nov 29, 2012 lovastatin is the first of a new class of cholesterol lowering drugs that competitively inhibit hmgcoa reductase. Indeed, lovastatin has been shown to interact synergis. Hydrolyzed in vivo to an active metabolite, simvastatin. Simvastatin is indicated for the treatment of hyperlipidemia to reduce elevated total cholesterol totalc, lowdensity lipoprotein cholesterol ldl. Following administration of lovastatin tablets the coefficient of variation, based on betweensubject variability, was approximately 40% for the area under the curve. Lowering of total and ldl cholesterol and triglycerides.
This makes lovastatin a promising drug to be administered as a cytostatic agent in conjunction with other cytotoxic agents. Mevacor lovastatin is a cholesterollowering medication called a statin prescribed to treat elevated blood cholesterol levels. This makes lovastatin a promising drug to be administered. Synthesis there have been numerous approaches to the total synthesis of lovastatin 810. May 24, 20 lovastatin belongs to a group of drugs called hmgcoa reductase inhibitors, also known as statins. Simvastatin mik733, synvinolin and zocor is mainly obtained by semisynthetic process, involving the chemical modification of lovastatin side chain hoffman et al. Lovastatin is a fungal polyketide employed as a cholesterollowering drug that inhibits 3shydroxy3methylglutarylcoenzyme. Atorvastatin lipitor by mcr acs medicinal chemistry letters.
Muscle pain and stiffness in the shoulder, neck and pelvis. Increased risk of myopathy andor rhabdomyolysis 1 339. Lovastatin mevacor is a statin medication used to lower cholesterol. Lovastatin information, side effects, warnings and recalls. Lovastatin, sold under the brand name mevacor among others, is a statin medication, to treat high blood cholesterol and reduce the risk of cardiovascular disease. F4655, f4658 this includes the treatment of primary hyperlipidemia fredrickson type iia, heterozygous familial and nonfamilial. Patchett, 1993, designed lovastatin 12 brenner et al. Lovastatin is used to lower the risk of stroke, heart attack, and other heart complications in people with diabetes, coronary heart disease, or other risk factors. Simvastatin is a lipidlowering agent derived synthetically from a fermentation product of the fungus aspergillus terreus. It works by decreasing the amount of cholesterol made in the body. Thus, hmgcoa reductase inhibition by lovastatin at the therapeutic dose used here did not change the steadystate rate of wholebody cholesterol synthesis. Lovastatin, monacolin j, monacolin l, and mevastatin can be produced by monascus ruber, penicillium brevicompactum, and aspergillus terreus 1, 36. Therapeutic class overview statins hmgcoa reductase. Lovastatin was not detected in any of the raw puerh tea samples without storage but was found in almost all the ripe puerh tea samples, with lovastatin contents ranging from 20.
Atorvastatin lipitor by mcr acs medicinal chemistry. Lovastatin is a fungal polyketide employed as a cholesterollowering drug that inhibits 3shydroxy3methylglutarylcoenzyme a hmgcoa reductase. This new drug decreases cholesterol synthesis and apolipoprotein b concentrations, and increases ldl receptor activity without adverse effects on other products in the cholesterol pathway. Pdf biosynthesis and biotechnological production of statins by. By controlling the rate of cholesterol production in the body, the medicine is effective in reducing total cholesterol, ldl cholesterol, and triglycerides, as well as increasing hdl cholesterol. Lovastatin is indicated as an adjunct to diet for the reduction of elevated totalc and ldlc levels in patients with primary hypercholesterolemia types iia and iib 2, when the response to diet. Lovastatin 57 belongs to the family of statins, a class of compounds that are important cholesterol lowering drugs fig. Thus, the 1,4 amido acid motif could easily be derived from an ugi adduct with the. The synthetic sequence is shown in the schemes below. Lovastatin may also be used for purposes not listed in this medication guide. Cholesterol is found exclusively in animals, hence it is. A major bulk of work in the synthesis of lovastatin was done by m. Chemical transformations of lovastatin 2 into simvastatin 3. A concise and convergent synthesis of the atorvastatin, the bestselling cardiovascular drug of all time, is presented.
The pharmacokinetic parameters in 12 hypercholesterolemic subjects. This enzyme catalyzes the conversion of hmgcoa to mevalonate, which is a cholesterol precursor. The initial derived mcr adduct can be considered as a synthetic hub to a vast diversity of other scaffolds. Research paper effects of lovastatin on mdamb231 breast. Lovastatin is used for the prevention of heart disease and the treatment of high cholesterol and high triglycerides. Lovastatin side effects, uses, dosage, overdose, pregnancy. Lovastatin is an inhibitor of the enzyme hydroxymethylglutaryl coenzyme a hmgcoa reductase mevalonate. Here we report the total synthesis of taxol by a convergent strategy, which opens a chemical pathway for the production of both the natural product itself and a variety of designed. Compactin, ml236b and cs 500 has methyl butyric side chain r 1 and has only hydrogen group on r 2. Inhibition of hmgcoa reductase decreases hepatic cholesterol synthesis, causing upregulation of lowdensity lipoprotein cholesterol ldlc receptors. Inhibition of dietary cholesterol absorption during. Lovastatin c24h36o5 cid 53232 structure, chemical names, physical and.
Lovastatin definition of lovastatin by medical dictionary. The story of lipitor a peek into the world of pharmaceutical process chemistry aman desai 7th feb. In filamentous fungi many secondary metabolites with complex chemical structure are synthesized via the polyketide pathway 15, 33, 37. Here we report the total synthesis of taxol by a convergent strategy, which opens a chemical pathway for the production of both the natural product itself and a variety of designed taxoids. It is an inactive prodrug, the methylated derivative of lovastatin, and like lovastatin, must be activated in the liver. It acts as a precursor for the synthesis of many steroids, vitamin d. The chapter describes the isolation and identification of lovastatin from the fermentation media.
When the cytostatic activity of lovastatin was compared among a variety of cell lines, the ic 50s were in the range of 0. By controlling the rate of cholesterol production in the body, the medicine is. Following administration of lovastatin tablets the coefficient of variation, based on betweensubject variability, was approximately 40% for the area under the curve auc of total inhibitory activity in the general circulation. Lovastatin is used in adults and children who are at least 10 years old. Altoprev lovastatin extendedrelease tablets description. Lovastatin is used along with a proper diet to help lower bad cholesterol and fats such as ldl, triglycerides and raise good cholesterol hdl in the blood. Zocor simvastatin dose, indications, adverse effects. If used concomitantly, do not exceed lovastatin dosage of 40 mg daily. In patients with heterozygous familial or polygenic nonfamilial hypercholesterolaemia. Hirama synthesized compactin and used one of the intermediates to follow a different path to get to lovastatin. This medication comes as a tablet and an extended release tablet to take by mouth. Lovastatin definition of lovastatin by the free dictionary. This enzyme catalyses the synthesis of mevalonate, which is the immediate precursor of cholesterol and is the target of all of the drugs classed as statins. The extendedrelease tablet usually is taken once a day at bedtime.
Lovastatin comes as a tablet and an extendedrelease longacting tablet to take by mouth. All the statin molecules reduce the cholestrol level by same mechanism, where they inhibit the hmgcoa reductase, an important precursor in the cholesterol synthesis. Microbial production and biomedical applications of lovastatin ncbi. Nov 11, 1988 a reduction in cholesterol synthesis by lovastatin has been subsequently confirmed in cell culture, animal studies and in humans.
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