Summary
Both conventional direct current (DC) and pulsedmode 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.
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References
Guy RH, Hadgraft J. Selection of drug candidates for transdermal drug delivery. In: Hadgraft J, Guy RH, eds. Transdermal drug delivery: Developmental issues and research initiatives. New York: Marcel Dekker, 1989:59–81.
Spieker C, Vetter H, Liedtke R, et al. Transdermal betablocker therapy in essential hypertension. Am J Hypertens 1988;1 (Suppl 3):199S-200S.
Singh J, Roberts MS. Transdermal delivery of drugs by iontophoresis: A review. Drug Des Delivery 1989;4:1–12.
Lawler JC, Davis MJ, Griffith EC. Electrical characteristics of the skin: The impedance of the surface sheath and deep tissues. J Invest Dermatol 1960;34:301–308.
Davis DR, Kennard DW. Influence of electric current on the skin. Nature 1962;193:1186–1187.
Okabe K, Yamaguchi H, Kawai Y. New iontophoretic transdermal administration of the beta-blocker metoprolol. J Controlled Release 1986;4:79–85.
Zakzewski CA, Li J K-J. Pulsed mode constant current iontophoretic transdermal metoprolol tartrate delivery in established acute hypertensive rabbits. J Controlled Release 1991;17:157–162.
Burnette RR. Iontophoresis. In: Hadgraft J, Guy RH, eds. Transdermal drug delivery: Developmental issues and research initiatives. New York: Marcel Dekker, 1989:247–291.
Flynn GL. Mechanism of percutaneous absorption from physicochemical evidence. In: Bronaugh RL, Maibach HI, eds. Percutaneous absorption: Mechanisms—methodology—drug delivery, 2nd ed. New York: Marcel Dekker, 1989:27–51.
Hansch C, Sammes PG, Taylor JB, eds. Comprehensive medicinal chemistry: The rational design, mechanistic studies, & therapeutic application of chemical compounds, Vol. 6. New York: Pergamon Press, 1990.
Teorell T. Transport processes and electrical phenomena in ionic membranes. Prog Biophys Mol Biol 1953;3:305–369.
Edelberg R. Electrical properties of skin. In: Elden HR, ed. Biophysical properties of the skin. New York: John Wiley & Sons, 1971:513–550.
Yamamoto T, Yamamoto Y. Electrical properties of the epidermal stratum corneum. Med Biol Eng 1976;14:151–158.
Rosell J, Colominas J, Riu P, et al. Skin impedance from 1 Hz to 1 MHz. IEEE Trans Biomed Eng 1988;35(8):649–651.
Foster SB, Kousch D. Adherence to therapy in hypertensive patients. Nurs Clin North Am 1981;16(2):331–341.
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Zakzewski, C.A., Amory, D.W., Jasaitis, D.K. et al. Iontophoretically enhanced transdermal delivery of an ACE inhibitor in induced hypertensive rabbits: Preliminary report. Cardiovasc Drug Ther 6, 589–595 (1992). https://doi.org/10.1007/BF00052560
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DOI: https://doi.org/10.1007/BF00052560