Evaluation of pharmacokinetics and pharmacodynamics of captopril from transdermal hydrophilic gels in normotensive rabbits and spontaneously hypertensive rats.

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.