ENHANCEMENT OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A (HMG-COA) REDUCTASE INHIBITOR EFFICACY THROUGH ADMINISTRATION OF A CONTROLLED-POROSITY OSMOTIC PUMP DOSAGE FORM

被引:35
作者
MCCLELLAND, GA
STUBBS, RJ
FIX, JA
POGANY, SA
ZENTNER, GM
机构
[1] INTERX RES CORP,MERCK SHARP & DOHME RES LABS,2201 W 21ST ST,LAWRENCE,KS 66047
[2] MERCK SHARP & DOHME LTD,W POINT,PA 19486
[3] UNIV KANSAS,DEPT PHARMACEUT CHEM,LAWRENCE,KS 66045
关键词
3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE (HMG-COA REDUCTASE) INHIBITOR; SIMVASTATIN; EXTENDED RELEASE; OSMOTIC PUMP; CHOLESTEROL LOWERING EFFICACY;
D O I
10.1023/A:1015899328105
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
An extended-release osmotic dosage form was designed for gastrointestinal delivery of the water-soluble tromethamine salt of the beta-hydroxyacid form of simvastatin, a potent HMG-CoA reductase inhibitor and cholesterol lowering agent. The cholesterol lowering efficacy and systemic plasma drug levels resulting from peroral administration of this dosage form, relative to a powder-filled capsule oral bolus, were evaluated in dogs. A twofold improvement in cholesterol lowering efficacy was realized with the controlled-release dosage form that was accompanied by a drug AUC and C(max) that were 67 and 16%, respectively, of those achieved with the bolus dosage form. These results suggest that extended-release dosage forms have the potential for a dose-sparing advantage in the administration of HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia.
引用
收藏
页码:873 / 876
页数:4
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