Rao P Rama, Reddy M Narender, Ramakrishna Sistla, Diwan Prakash V
Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad, AP, India.
Eur J Pharm Biopharm. 2003 Jul;56(1):81-5. doi: 10.1016/s0939-6411(03)00038-9.
The purpose of this study was the in vivo evaluation of orally and transdermally administered propranolol hydrochloride in rabbits. Transdermal patches of propranolol hydrochloride (PPN) were formulated employing ethyl cellulose and polyvinylpyrrolidone as film formers. The pharmacodynamic (PD) and pharmacokinetic (PK) performance of PPN 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 PK parameters such as maximum plasma concentration (C(max)), time for peak plasma concentration (t(max)), mean residence time (MRT) and area under the curve (AUC(0-alpha)) were significantly (P<0.01) different following transdermal administration compared to oral administration. The terminal elimination half-life (t(1/2)) of transdermally delivered PPN was found to be similar to that following oral administration. In contrast to oral delivery, a sustained therapeutic activity was observed over a period of 24 h after transdermal administration compared to oral administration. The relative bioavailability of PPN was increased about fivefold to sixfold after transdermal administration as compared to oral delivery. This may be due to the avoidance of first pass effect of PPN. The sustained therapeutic activity was due to the controlled release of drug into systemic circulation following transdermal administration.
本研究的目的是对家兔口服和经皮给药的盐酸普萘洛尔进行体内评价。以乙基纤维素和聚乙烯吡咯烷酮作为成膜剂，制备了盐酸普萘洛尔（PPN）透皮贴剂。将PPN经皮给药后的药效学（PD）和药代动力学（PK）性能与口服给药进行了比较。本研究采用随机交叉设计，在雄性新西兰白化兔中进行。与口服给药相比，经皮给药后的PK参数，如最大血浆浓度（C(max)）、血浆浓度达峰时间（t(max)）、平均驻留时间（MRT）和曲线下面积（AUC(0-α)）有显著差异（P<0.01）。经皮给药的PPN的末端消除半衰期（t(1/2)）与口服给药后的相似。与口服给药相比，经皮给药后在24小时内观察到持续的治疗活性。与口服给药相比，PPN经皮给药后的相对生物利用度提高了约五倍至六倍。这可能是由于避免了PPN的首过效应。持续的治疗活性是由于经皮给药后药物向体循环的控释。
