Zakzewski C A, Amory D W, Jasaitis D K, Li J K
Department of Biomedical Engineering, Rutgers, State University of New Jersey, Piscataway.
Cardiovasc Drugs Ther. 1992 Dec;6(6):589-95. doi: 10.1007/BF00052560.
Both conventional direct current (DC) and pulsed-mode DC constant-current iontophoresis were used to investigate enhanced transdermal delivery of the angiotensin-converting enzyme (ACE) inhibitor captopril to rabbits with acutely induced hypertension. Passive transdermal captopril administration and pulsed DC constant-current iontophoresis of the vehicle were studied as control experimentation. Mean arterial pressure (MAP) was not significantly (p > 0.05) altered following passive transdermal delivery of captopril (n = 4) or after iontophoretic delivery of the vehicle alone (n = 4). Pressure reduction was evident within 10 minutes of iontophoretic enhancement of transdermal captopril delivery. DC mode constant-current (n = 4) iontophoretic transdermal captopril administration caused MAP to fall by 21% from a mean hypertensive level of 66 +/- 5 mmHg to a mean post-treatment level of 52 +/- 6 mmHg (p < 0.05) within 60 minutes. Pulsed DC mode constant-current (n = 4) iontophoresis of captopril caused mean MAP to fall on average by 27% from 62 +/- 6 to 45 +/- 5 mmHg (p < 0.05), also within 60 minutes. This paper provides the first report on the enhanced efficiency during iontophoretic delivery of an ACE inhibitor. We have concluded that both modes of constant-current iontophoresis of captopril offer a safe and effective means of pressure reduction in rabbits with induced hypertension and that there is no significant difference in efficacy between the two forms of enhanced delivery. These results have potential applications for enhanced transdermal delivery of ACE inhibitors in humans.
采用传统直流电（DC）和脉冲模式DC恒流离子电渗疗法，研究血管紧张素转换酶（ACE）抑制剂卡托普利经皮给药增强对急性高血压兔的治疗效果。作为对照实验，研究了卡托普利的被动经皮给药以及载体的脉冲DC恒流离子电渗疗法。卡托普利被动经皮给药（n = 4）或单独进行载体离子电渗给药后（n = 4），平均动脉压（MAP）无显著变化（p > 0.05）。在离子电渗增强卡托普利经皮给药后10分钟内，血压降低明显。DC模式恒流（n = 4）离子电渗经皮给予卡托普利，导致MAP在60分钟内从平均高血压水平66±5 mmHg下降21%，至平均治疗后水平52±6 mmHg（p < 0.05）。卡托普利的脉冲DC模式恒流（n = 4）离子电渗疗法使平均MAP在60分钟内也从62±6 mmHg平均下降27%，至45±5 mmHg（p < 0.05）。本文首次报道了ACE抑制剂离子电渗给药效率的提高。我们得出结论，卡托普利的两种恒流离子电渗模式均为诱导高血压兔提供了一种安全有效的降压方法，且两种增强给药形式在疗效上无显著差异。这些结果对人类增强ACE抑制剂经皮给药具有潜在应用价值。
