title: Plasma free captopril concentrations during short and long term treatment with oral captopril for heart failure.
abstract: Plasma free captopril concentrations and haemodynamic response to captopril were studied in 20 patients with severe chronic heart failure. A 25 mg oral dose of captopril produced a 36% reduction in systemic vascular resistance, with individual responses varying from 13% to 64%. Mean systemic pressure fell by 20% and cardiac output rose 28%. The absorption of captopril was rapid. Peak plasma free captopril concentration occurred at 45 minutes after the dose and was followed by a smaller second peak. Peak plasma free captopril concentrations varied more than 20-fold but did not correlate with the maximal reduction in systemic vascular resistance. Elimination half life was seven hours. Fourteen patients were restudied after 1-2 months of captopril treatment and 12 showed symptomatic benefit. There was a sustained improvement in haemodynamic state and in non-invasive indices of myocardial function. During long term treatment the predose plasma free captopril concentration correlated well with dosage, but steady state captopril concentrations did not show a significant relation with haemodynamic response. On a dosage regimen of 25-50 mg three times daily the morning predose plasma free captopril concentration and plasma renin activity were relatively low and suggested that maximal inhibition of the renin-angiotensin system was not maintained throughout the dosage interval.
mesh_terms: D000368:Aged; D002216:Captopril / Q000097:blood* / Q000627:therapeutic use; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives*; D012083:Renin / Q000097:blood; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D011392:Proline; D002216:Captopril; D012083:Renin