Iontophoretically enhanced transdermal delivery of an ACE inhibitor in induced hypertensive rabbits: preliminary report.
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.
Zakzewski
C A
CA
Department of Biomedical Engineering, Rutgers, State University of New Jersey, Piscataway.
Amory
D W
DW
Jasaitis
D K
DK
Li
J K
JK
D000279:Administration, Cutaneous; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007478:Iontophoresis; D008297:Male; D011817:Rabbits
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril