A pharmacokinetic and pharmacodynamic evaluation of buffered sublingual captopril in patients with congestive heart failure

Objective: The pharmacokinetics and pharmacodynamics of buffered sublingual captopril were assessed in patients with congestive heart failure (CHF). Methods: The study was carried out in a randomised single-blind cross-over fashion (n = 6, 4 males and 2 females) and involved two study days, at least 7 days apart. Baseline measurements were carried out for plasma renin activity (PRA), blood pressure (B.P.) and heart rate (H.R.). Captopril (12.5 mg) was administered sublingually with dibasic potassium phosphate which maintained salivary pH at 7, or perorally with 100 ml of water. Further B.P., H.R. measurements and venous blood samples were taken over a 3 hour period post-drug administration. Blood samples were analysed for captopril and PRA levels. Results: t(max) after buffered sublingual administration of captopril, which ranged from 40-60 min (median = 40 min), was significantly shorter than after peroral administration (range 60-120 min; median = 90 min). C-max was slightly greater after buffered sublingual than after peroral administration with mean values of 108.2 vs. 94.0 ng . ml(-1). AUC values were similar after both routes of administration. Systolic and diastolic B.P. vs. time profiles for each administration method were significantly different i.e. sublingual administration produced an earlier reduction in B.P., however, HR did not differ significantly between the two routes. Conclusion: The data indicate that this novel administration method of captopril leads to an increased rate, but an unchanged extent of captopril absorption, suggesting a modest therapeutic advantage with the use of buffered sublingual captopril if a rapid reduction in blood pressure is required.