title: Bioavailability assessment of hydroxymethylglutaryl coenzyme A reductase inhibitor utilizing pulsatile drug delivery system: a pilot study.
abstract: Chronotherapy or pulsatile drug delivery system could be achieved by increasing drug plasma concentration exactly at the time of disease incidence. Cholesterol synthesis shows a circadian rhythm being high at late night and early in the morning. Simvastatin (SIM) inhibits hydroxymethylglutaryl coenzyme A reductase, which is responsible for cholesterol synthesis. In this study, SIM lipid-based formulation filled in gelatin capsules and coated with aqueous Eudragit® S100 dispersion was prepared for chronotherapeutic treatment of hypercholesterolemia. The pharmacokinetic parameters of SIM capsules were studied in human volunteers after a single oral dose and compared with that of Zocor® tablets as a reference in a randomized cross-over study. Pharmacokinetic parameters such as AUC0-∞, Cmax, Tmax, t1/2and elimination rate constant were determined from plasma concentration-time profile for both formulations. The tested formulation had the ability to delay drug absorption and provide higher drug concentrations from 3 up to 10 h after oral administration compared to that of commercial tablets. The data in this study revealed that the prepared formulation could be effective in chronotherapeutic treatment of hypercholesterolemia. Moreover, the tested formulation was found to enhance SIM bioavailability by 29% over the reference tablets.
authors.affiliation: a Department of Pharmaceutics , College of Pharmacy, King Saud University , Saudi Arabia and.|b Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt.
authors.forename: Ehab I
authors.initials: EI
authors.lastname: Taha
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018592:Cross-Over Studies; D016503:Drug Delivery Systems / Q000379:methods; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy; D008055:Lipids / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019821:Simvastatin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013607:Tablets / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D002214:Capsules; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D013607:Tablets; D005780:Gelatin; D019821:Simvastatin
keywords: Bioavailability; chronotherapy; colon delivery; lipid formulation; pulsatile system; simvastatin