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Simvastatin Simvastatin reduces cholesterol by inhibiting the conversion of HMG-CoA to mevalonate, an early stepin the biosynthetic pathway for cholesterol. In addition, simvastatin reduces VLDL and TG and increases HDL-C. Pharmacokinetics Text Continues Below
Absorption VYTORIN VYTORIN is bioequivalent to coadministered ezetimibe and simvastatin. After oral administration, ezetimibe is absorbed and extensively conjugated to a pharmacologically active phenolic glucuronide (ezetimibe-glucuronide). Effect of Food on Oral Absorption Concomitant food administration (high-fat or non-fat meals) had no effect on the extent of absorption of ezetimibe when administered as 10-mg tablets. The Cmax value of ezetimibe was increased by 38% with consumption of high-fat meals. Simvastatin Relative to the fasting state, the plasma profiles of both active and total inhibitors of HMG-CoAreductase were not affected when simvastatin was administered immediately before an American Heart Association recommended low-fat meal.
Distribution Ezetimibe Ezetimibe and ezetimibe-glucuronide are highly bound (>90%) to human plasma proteins. Simvastatin Both simvastatin and its ß-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins. When radio labeled simvastatin was administered to rats, simvastatin-derived radioactivity crossed the blood-brain barrier. Metabolism and Excretion Ezetimibe Ezetimibe is primarily metabolized in the small intestine and liver via glucuronide conjugation with subsequent biliary and renal excretion. Minimal oxidative metabolism has been observed in all species evaluated. In humans, ezetimibe is rapidly metabolized to ezetimibe-glucuronide. Ezetimibe and ezetimibe glucuronide are the major drug-derived compounds detected in plasma, constituting approximately 10 to 20% and 80 to 90% of the total drug in plasma, respectively. Both ezetimibe and ezetimibe-glucuronideare slowly eliminated from plasma with a half-life of approximately 22 hours for both ezetimibe andezetimibe-glucuronide. Plasma concentration-time profiles exhibit multiple peaks, suggesting enterohepatic recycling. Following oral administration of 14C-ezetimibe (20 mg) to human subjects, total ezetimibe (ezetimibe +ezetimibe-glucuronide) accounted for approximately 93% of the total radioactivity in plasma. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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