Wu P C, Huang Y B, Chang J J, Chang J S, Tsai Y S
School of Pharmacy, Kaohsiung Medical University, 100 Shih-Chen 1st R.D., 807, Kaohsiung, Taiwan, ROC.
Int J Pharm. 2000 Nov 19;209(1-2):87-94. doi: 10.1016/s0378-5173(00)00557-3.
The purpose of this investigation was to assess the pharmacokinetics (plasma concentration) and pharmacodynamics (heart rate, blood pressure (BP), and plasma renin activity (PRA)) of captopril experimental gel in normotensive rabbits and spontaneously hypertensive rats (SHRs) by reference to a short duration intravenous administration of the drug. In normotensive rabbits, the blood concentration versus time course of captopril after transdermal administration could be described well by a two-compartment model, and the maximum plasma concentration (5. 68+/-2.05 microg ml(-1)) was achieved in about 7 h. The increase in plasma captopril concentration led to increases in PRA and reductions in BP. A simple E(max) model adequately described the relationship between the percentage change of mean blood pressure (MBP) and the blood concentration of the captopril. The maximum reduction in MBP (E(max)) was 36.23% and the concentration at half maximum effect (EC(50)) was 0.24 microg ml(-1). The captopril was continuously released from the gel formulation and protected the SHRs in lower BP throughout the period of transdermal therapy. These results indicated that the development of captopril transdermal drug delivery system was possible. Further research was warranted on a modified formulation of captopril, which was optimized for transdermal delivery of the drug.
本研究的目的是通过参考卡托普利短时间静脉给药情况，评估卡托普利实验性凝胶在正常血压兔和自发性高血压大鼠（SHRs）体内的药代动力学（血浆浓度）和药效学（心率、血压（BP）及血浆肾素活性（PRA））。在正常血压兔中，经皮给药后卡托普利的血药浓度-时间过程可用二室模型很好地描述，约7小时达到最大血浆浓度（5.68±2.05微克/毫升）。血浆卡托普利浓度的升高导致PRA升高和BP降低。一个简单的E(max)模型能充分描述平均血压（MBP）变化百分比与卡托普利血药浓度之间的关系。MBP的最大降低值（E(max)）为36.23%，半数最大效应浓度（EC(50)）为0.24微克/毫升。卡托普利从凝胶制剂中持续释放，并在整个经皮治疗期间使SHRs的血压保持在较低水平。这些结果表明卡托普利经皮给药系统的开发是可行的。有必要对卡托普利的改良制剂进行进一步研究，该制剂经优化用于药物的经皮递送。
