Enhancement of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor efficacy through administration of a controlled-porosity osmotic pump dosage form

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 level...

Full description

Saved in:
Bibliographic Details
Published in:Pharmaceutical research 1991-07, Vol.8 (7), p.873-876
Main Authors: MCCLELLAND, G. A, STUBBS, R. J, FIX, J. A, POGANY, S. A, ZENTNER, G. M
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cholesterol - blood
Chromatography, High Pressure Liquid
Delayed-Action Preparations
Dogs
General pharmacology
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lovastatin - administration & dosage
Lovastatin - analogs & derivatives
Lovastatin - pharmacokinetics
Medical sciences
Osmotic Pressure
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Simvastatin
Solubility
Tablets
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 Cmax 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.
ISSN:0724-8741
1573-904X
DOI:10.1023/A:1015899328105