Captopril: pharmacokinetics, antihypertensive and biological effects in hypertensive patients.

Abstract

1 The kinetics of captopril plasma levels and of the drug-induced plasma converting enzyme activity (PCEA), plasma renin activity (PRA) and diastolic blood pressure (DBP) modifications were studied over 24 h after oral administration of captopril, 1 mg/kg, to ten hypertensive patients. 3 The onset of PCEA inhibition and of DBP decrease closely followed the rise of captopril's plasma levels, while that of PRA increase was delayed. In contrast, while captopril rapidly disappeared from plasma, its biological and antihypertensive effects were long-lasting. 4 The lack of correlation between the relative bioavailability of captopril and the induced reduction in DBP (evaluated by the corresponding AUCs) suggests that free unchanged captopril plasma monitoring is not an adequate indicator of hypertensive patients' potential responsiveness to captopril's blood pressure lowering effects.

Influence of chronic renal failure on captopril pharmacokinetics and clinical and biological effects in hypertensive patients.

“…The method used derived from that initially developed by Kawahara et al (1981) has previously been described (Richer et al, 1984). In brief, whole free form of unchanged captopril was trapped with p-BPB, which was used as a coupling reagent for the thiol function, thus ensuring its stability, and the addition product was evaluated by high pressure liquid chromatography (h.p.l.c.).…”

“…(Kripalani et al, 1980;Onoyama et al, 1981;Duchin et al, 1982) or in hypertensive subjects (tmax: 0.6-0.9 h; T½/2: 0.6-1.6 h) (Jarrott et al, 1981(Jarrott et al, , 1982Richer et al, 1984) whatever the one- (Onoyama et al, 1981;Richer et al, 1984) or two-compartment (Duchin et al, 1982) (Duchin et al, 1982) but at concentrations below its plasma detection threshold. Hence, these metabolites could in case of accumulation prolong the duration of captopril biological and clinical effects.…”

Captopril pharmacokinetics [letter]

“…These variations were independent of body weight and were attributed to variability of theophylline clearance. The bioavailability of slow-release choline theophyllinate has also been observed to change after repeated dosing (Leung et al, 1978;Dahlqvist & Billing, 1983) suggesting possible saturation of the metabolic breakdown pathway of theophylline in the liver (Trembath et al, 1979 Guidicelli et al (1984) and Richer et al (1984), they found a linear correlation between CLt.tai of captopnil and CL of creatinine. These data are in a better agreement with the potentiating effects of chronic renal failure on captopnl-induced plasma converting enzyme activity blockade and blood pressure reduction found by Guidicelli et al(1984), and Richer et al (1984) …”

Effect of captopril on functional, physiological and biochemical outcome criteria in aged heart failure patients.

“…Patients not already in hospital were admitted for the introduction of captopril, which was started at a dose of 6.25 mg twice (10.00 and 22.00 h) daily. In the absence of adverse effects, the dosage was doubled daily until either (i) there was 80% or more inhibition of ACE activity at 3 h after a morning dose Richer et al, 1984), by comparison with the activity immediately before the first dose, or (ii) the ACE activity had fallen below the limit of detection of the assay (12 iu l-1) (Maguire & Price, 1985), at this time. The maximum dosage used was 50 mg twice daily.…”