COMPARATIVE BIOAVAILABILITY EVALUATION OF FLUVASTATIN SODIUM AFTER ORAL AND TRANSDERMAL ADMINISTRATION IN RABBITS

Membrane-moderated transdermal systems of   Fluvastatin Sodium liposomes were prepared by incorporating the drug reservoir within a shallow compartment moulded from a drug-impermeable backing membrane and 2% w/v cellulose acetate rate-controlling membrane . The pharmacokinetic performance of  Fluvastatin Sodium following transdermal administration was compared with that of oral administration. This study was carried out in a randomized cross-over design in male New Zealand albino rabbits. The estimation of  Fluvastatin Sodiumin plasma was carried out by LC-MS/MS method. The parameters such as maximum plasma concentration (C max), time for peak plasma concentration (t max), mean residence time (MRT) and area under curve (AUC 0 - ∞) were significantly (P< 0.001) differed following transdermal administration compared to oral administration. The relative bioavailability of  Fluvastatin Sodium was increased about nine fold after transdermal administration as compared to oral delivery. This may be due to the avoidance of first pass effect of  Fluvastatin Sodium. The concentration of  Fluvastatin Sodium in plasma was found to be stabilized and maintained in a narrow range over the study period up to 24 hrs for transdermal formulation where as the concentration was decreased rapidly up on oral administration. It was concluded that the relative rate of extensive first pass metabolism was significantly reduced in transdermal administration, resulted in increased relative bioavailability and reduced frequency of administration.

Keywords:  Fluvastatin Sodium,  Liposomes, Transdermal systems, LC-MS/MS, In-vivo studies.