ROSUVASTATIN + VITAMIN D3
BRAND NAME:-Z-ROSU D (ROSUVASTATIN + VITAMIN D3)
COMPOSITION: – ROSUVASTATIN + VITAMIN D3
PACKING:- 10 X 10
Rosuvastatin is an antilipemic agent that competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reducuase catalyzes the conversion of HMG-CoA to mevalonic acid, the rate-limiting step in cholesterol biosynthesis. Rosuvastatin belongs to a class of medications called statins and is used to reduce plasma cholesterol levels and prevent cardiovascular disease.
Vitamin D refers to a group of fat-soluble secosteroids responsible for enhancing intestinal absorption of calcium, iron, magnesium, phosphate, and zinc. In humans, the most important compounds in this group are vitamin D3 (also known as cholecalciferol) and vitamin D2 (ergocalciferol). Cholecalciferol and ergocalciferol can be ingested from the diet and from supplements. Very few foods contain vitamin D; synthesis of vitamin D (specifically cholecalciferol) in the skin is the major natural source of the vitamin. Dermal synthesis of vitamin D from cholesterol is dependent on sun exposure (specifically UVB radiation).
PHARMACODYNAMICS: – Rosuvastatin is a synthetic, enantiomerically pure antilipemic agent. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality.
MECHANISM OF ACTION: –Rosuvastatin is a competitive inhibitor of HMG-CoA reductase. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis. Rosuvastatin acts primarily in the liver. Decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increases hepatic uptake of LDL. Rosuvastatin also inhibits hepatic synthesis of very low density lipoprotein (VLDL). The overall effect is a decrease in plasma LDL and VLDL. In vitro and in vivo animal studies also demonstrate that rosuvastatin exerts vasculoprotective effects independent of its lipid-lowering properties. Rosuvastatin exerts an anti-inflammatory effect on rat mesenteric microvascular endothelium by attenuating leukocyte rolling, adherence and transmigration (PMID: 11375257). The drug also modulates nitric oxide synthase (NOS) expression and reduces ischemic-reperfusion injuries in rat hearts (PMID: 15914111). Rosuvastatin increases the bioavailability of nitric oxide (PMID: 11375257, 12031849, 15914111) by upregulating NOS (PMID: 12354446) and by increasing the stability of NOS through post-transcriptional polyadenylation (PMID: 17916773). It is unclear as to how rosuvastatin brings about these effects though they may be due to decreased concentrations of mevalonic acid.
MECHANISM OF ACTION: –Vitamin D is carried in the bloodstream to the liver, where it is converted into the prohormone calcidiol. Circulating calcidiol may then be converted into calcitriol, the biologically active form of vitamin D, in the kidneys. Following the final converting step in the kidney, calcitriol is released into the circulation. By binding to vitamin D-binding protein, a carrier protein in the plasma, calcitriol is transported to various target organs. In addition to the kidneys, calcitriol is also synthesized by monocyte-macrophages in the immune system. When synthesized by monocyte-macrophages, calcitriol acts locally as a cytokine, defending the body against microbial invaders by stimulating the innate immune system.
Whether it is made in the skin or ingested, cholecalciferol is hydroxylated in the liver at position 25 (upper right of the molecule) to form 25-hydroxycholecalciferol (calcidiol or 25(OH)D). This reaction is catalyzed by the microsomal enzyme vitamin D 25-hydroxylase, which is produced by hepatocytes. Once made, the product is released into the plasma, where it is bound to an α-globulin, vitamin D-binding protein.
Calcidiol is transported to the proximal tubules of the kidneys, where it is hydroxylated at the 1-α position (lower right of the molecule) to form calcitriol (1,25-dihydroxycholecalciferol and abbreviated to 1,25(OH)2D). This product is a potent ligand of the vitamin D receptor, which mediates most of the physiological actions of the vitamin. The conversion of calcidiol to calcitriol is catalyzed by the enzyme 25-hydroxyvitamin D3 1-alpha-hydroxylase, the levels of which are increased by parathyroid hormone (and additionally by low calcium or phosphate).
· ABSORPTION: –Bioavailability is approximately 20%. Peak plasma concentrations were reached 3 to 5 hours following oral dosing. Both Cmax and AUC increased in approximate proportion to CRESTOR dose. Food has no effect on the AUC of rosuvastatin.
· VOLUME OF DISTRIBUTION: –134 L [steady-state]
· PROTEIN BINDING: –88% bound to plasma proteins (mostly albumin). Binding is reversible and independent of plasma concentrations.
· METABOLISM: –Not extensively metabolized. Only ~10% is excreted as metabolite. Cytochrome P450 (CYP) 2C9 is primarily responsible for the formation of rosuvastatin’s major metabolite, N-desmethylrosuvastatin. N-desmethylrosuvastatin has approximately 50% of the pharmacological activity of its parent compound in vitro. Rosuvastatin clearance is not dependent on metabolism by cytochrome P450 3A4 to a clinically significant extent. Rosuvastatin accounts for greater than 90% of the pharmacologic action. Inhibitors of CYP2C9 increase the AUC by less than 2-fold. This interaction does not appear to be clinically significant.
· ROUTE OF ELIMINATION: – Rosuvastatin is not extensively metabolized; approximately 10% of a radiolabeled dose is recovered as metabolite. Following oral administration, rosuvastatin and its metabolites are primarily excreted in the feces (90%). After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route.
· HALF-LIFE: -19 hours
· TOXICITY: – Generally well-tolerated. Side effects may include myalgia, constipation, asthenia, abdominal pain, and nausea. Other possible side effects include myotoxicity (myopathy, myositis, rhabdomyolysis) and hepatotoxicity. To avoid toxicity in Asian patients, lower doses should be considered.
· ABSORPTION: –Well absorbed from the GI tract. Presence of bile is essential for adequate intestinal absorption. Hence absorption may be decreased in patients with decreased fat absorption.
· DISTRIBUTION: – Bound to a specific α-globulin. Can be stored in adipose & muscle tissue for long periods of time. Slowly released from storage sites & skin where it is formed in the presence of sunlight or uv light. May distribute into breast milk.
· METABOLISM: – Hydroxylated in the liver by the enzyme vitamin D 25-hydroxylase to form 25-hydroxycholecalciferol (calcifediol). Further hydroxylated in the kidneys by the enzyme vitamin D1-hydroxylase to form the active metabolites 1, 25-dihydroxycholecalciferol (calcitriol). Further metabolism also occurs in the kidneys, including the formation of the 1, 24, 25-trihydroxy derivatives.
· EXCRETION: – Mainly in the bile &feces with only small amounts appearing in urine.
· Used as an adjunct to dietary therapy to treat primary hyperlipidemia (heterozygous familial and nonfamilial), mixed dyslipidemia and hypertriglyceridemia.
· Also indicated for homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies or when other such therapies are not available.
· Furthermore, it is used to slow the progression of atherosclerosis and for primary prevention of cardiovascular disease.
· Atherosclerosis, High Cholesterol,
· Familial Heterozygous, Familial Homozygous,
· Hyperlipoproteinemia, Hyperlipoproteinemia Type IIa, Elevated LDL, Hyperlipoproteinemia Type IIb, Elevated LDL VLDL,
· Hyperlipoproteinemia Type III, Elevated beta-VLDL IDL, Hyperlipoproteinemia Type IV, Elevated VLDL,
· Prevention of Cardiovascular Disease.
· Low levels of phosphate in the blood due to an inherited disorder called familial hypophosphatemia. Taking vitamin D (calcitriol or dihydrotachysterol) by mouth along with phosphate supplements is effective for treating bone disorders in people with low levels of phosphate in the blood.
· Low levels of phosphate in the blood due to a disease called Fanconi syndrome. Taking vitamin D (ergocalciferol) by mouth is effective for treating low levels of phosphate in the blood due to a disease called Fanconi syndrome.
· Low blood calcium levels due to low parathyroid hormone levels. Low levels of parathyroid hormone can cause calcium levels to become too low. Taking vitamin D (dihydrotachysterol, calcitriol, or ergocalciferol) by mouth is effective for increasing calcium blood levels in people with low parathyroid hormone levels.
· Softening of the bones (osteomalacia). Taking vitamin D (cholecalciferol) is effective for treating softening of the bones. Also, taking vitamin D (calcifediol) is effective for treating softening of the bones due to liver disease. In addition, taking vitamin D (ergocalciferol) is effective for treating softening of the bones caused by medications or poor absorption syndromes.
· Psoriasis. Applying vitamin D or calcipotriene (a synthetic form of vitamin D) to the skin treats psoriasis in some people. Applying vitamin D to the skin together with cream containing drugs called corticosteroids seems to be more effective for treating psoriasis than using just vitamin D or the corticosteroid creams alone.
· A bone disorder called renal osteodystrophy, which occurs in people with kidney failure. Taking vitamin D (calcifediol) by mouth manages low calcium levels and prevents bone loss in people with kidney failure. However, vitamin D does not appear to reduce the risk of death or bone pain in people with kidney failure.
· Rickets. Vitamin D is effective for preventing and treating rickets. A specific form of vitamin D, calcitriol, should be used in people with kidney failure.
· Vitamin D deficiency. Vitamin D is effective for preventing and treating vitamin D deficiency.