A PHARMACOKINETIC AND PHARMACODYNAMIC EVALUATION OF BUFFERED SUBLINGUAL CAPTOPRIL IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Objective: The pharmacokinetics and pharmacodynamics of buffered subli ngual captopril were assessed in patients with congestive heart failur e (CHF). Methods: The study was carried out in a randomised single-bli nd 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 r ate (H.R.). Captopril (12.5 mg) was administered sublingually with dib asic potassium phosphate which maintained salivary pH at 7, or peroral ly with 100 ml of water. Further B.P., H.R. measurements and venous bl ood samples were taken over a 3 hour period post-drug administration. Blood samples were analysed for captopril and PRA levels. Results: t(m ax) after buffered sublingual administration of captopril, which range d from 40-60 min (median = 40 min), was significantly shorter than aft er peroral administration (range 60-120 min; median = 90 min). C-max w as slightly greater after buffered sublingual than after peroral admin istration with mean values of 108.2 vs. 94.0 ng . ml(-1). AUC values w ere similar after both routes of administration. Systolic and diastoli c B.P. vs. time profiles for each administration method were significa ntly different i.e. sublingual administration produced an earlier redu ction in B.P., however, HR did not differ significantly between the tw o routes. Conclusion: The data indicate that this novel administration method of captopril leads to an increased rate, but an unchanged exte nt of captopril absorption, suggesting a modest therapeutic advantage with the use of buffered sublingual captopril if a rapid reduction in blood pressure is required.