Enhanced bioavailability of atenolol by transdermal administration of the ethylene-vinyl acetate matrix in rabbits.
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.
College of Pharmacy, Chonnam National University, Gwangju, South Korea.
Sang Chul
SC
Shin
Jun Shik
JS
Choi
D000279:Administration, Cutaneous; D000818:Animals; D001262:Atenolol / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D004357:Drug Synergism; D008297:Male; D011145:Polyvinyls / Q000008:administration & dosage*; D011817:Rabbits
D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; D001262:Atenolol