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Author: Admin | 2025-04-28
With rosuvastatin calcium tablets [see ADVERSE REACTIONS]. Patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels [see WARNINGS AND PRECAUTIONS]. Pregnancy [see Use in Specific Populations]. Lactation. Limited data indicate that rosuvastatin is present in human milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require rosuvastatin treatment should not breastfeed their infants [see Use in Specific Populations]. Clinical Pharmacology for Rosuvastatin Calcium TabletsMechanism Of ActionRosuvastatin calcium is a selectiveand competitive inhibitor of HMG-CoA reductase, the ratelimiting enzyme that converts 3-hydroxy-3-methylglutarylcoenzyme A to mevalonate, a precursor of cholesterol. In vivo studies inanimals, and in vitro studies in cultured animal and human cells have shown rosuvastatinto have a high uptake into, and selectivity for, action in the liver, thetarget organ for cholesterol lowering. In in vivo and in vitro studies,rosuvastatin produces its lipidmodifying effects in twoways. First, it increases the number of hepatic LDL receptors on the cellsurface to enhance uptake and catabolism of LDL. Second,rosuvastatin inhibits hepatic synthesis of VLDL, which reduces the total numberof VLDL and LDL particles.PharmacokineticsAbsorptionIn clinical pharmacology studiesin man, peak plasma concentrations of rosuvastatin were reached 3 to 5 hoursfollowing oral dosing. Both Cmax and AUC increased in approximate proportion torosuvastatin calcium dose. The absolute bioavailability of rosuvastatin is approximately20%.Administration of rosuvastatincalcium with food did not affect the AUC of rosuvastatin.The AUC of rosuvastatin does notdiffer following evening or morning drug administration.DistributionMean volume of distribution atsteady-state of rosuvastatin is approximately 134 liters. Rosuvastatin is 88%bound to plasma proteins, mostly albumin. This binding is reversible andindependent of plasma concentrations.MetabolismRosuvastatin is not extensivelymetabolized; approximately 10% of a radiolabeled dose is recovered as metabolite.The major metabolite is N-desmethyl rosuvastatin, which is formed principallyby cytochrome P450 \ 2C9, and in vitro studies have demonstrated thatN-desmethyl rosuvastatin has approximately one-sixth to one-half the HMG-CoAreductase inhibitory activity of the parent compound. Overall, greater than 90%of active plasma HMG-CoA reductase inhibitory activity is accounted for by theparent compound.ExcretionFollowing oral administration,rosuvastatin and its metabolites are primarily excreted in the feces (90%). Theelimination half-life (t½) of rosuvastatin is approximately 19 hours.After an intravenous
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