Enhanced bioavailability of atenolol by transdermal administration of the ethylene-vinyl acetate matrix in rabbits

Abstract

The pharmacokinetics and bioavailability of atenolol, a antihypertensive, were studied to determine the feasibility of enhanced transdermal delivery of atenolol from the ethylene-vinyl acetate (EVA) matrix system containing polyoxyethylene-2-oleyl ether as an enhancer in rabbits. The atenolol-EVA matrix (20 mg/kg) was applied to abdominal skin of rabbits. Blood samples were collected via the femoral artery for 32 h and the plasma concentrations of atenolol were determined by high-performance liquid chromatography. Pharmacokinetic parameters was calculated using Lagran computer program. The area under the curve (AUC) was significantly higher in the enhancer group (12,402±3061 ng/ml·h) than that in the control group (8507±2092 ng/ml·h), showing about 46% increased bioavailability ( P<0.05). The average C max was increased in the enhancer group (1361±340 ng/ml) compared with the control group (1168±293 ng/ml), but not significantly. The T max was significantly decreased in the enhancer group (1.3±0.36 h) compared with the control group (2.0±0.51 h). The elimination time (t 1/2) and mean residence time were significantly increased in the transdermal group compared with the IV group. The absolute bioavailability was 19.7% in the control group, 28.6% in the enhancer group and 77.4% in the oral administration group compared with IV the group. As the atenolol-EVA matrix containing polyoxyethylene-2-oleyl ether as an enhancer and tributyl citrate as a plasticizer was administered to rabbits via the transdermal routes, the relative AUC% increased about 1.46-fold compared to the control group, showing a relatively constant, sustained blood concentration with minimal fluctuation. The results of this study show that atenolol-EVA matrix could be developed as a transdermal delivery system providing sustained plasma concentration.