Effect of captopril on proteins and peptide hormones (original) (raw)
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Captopril: pharmacokinetics, antihypertensive and biological effects in hypertensive patients
British Journal of Clinical Pharmacology, 1984
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. 2 Free unchanged captopril pharmacokinetic parameters were: t1, _ 0.45 + 0.06 h; tmax:
American Heart Journal, 1982
Twelve patients with severe chronic congestive heart failure (CHF) underwent simultaneous evaluation of the pharmacokinetic, pharmacodynamic, and neurohumoral actions of a single 25 mg oral dose of the angiotensin-converting enzyme (ACE) inhibitor captopril (CPT). Following drug administration, which raised plasma renin activity (PRA) and thereby indicated significant ACE inhibition, both free (unchanged) and total CPT (including active metabolites) were detectable in the blood with 40 minutes and peak blood levels of the agent were recorded 1 hour after CPT. Total CPT concentration was higher and persisted longer than free CPT, which became virtually nondetectable 8 hours after ingestion. Concomitantly, left ventricular function was markedly augmented by the oral ACE inhibition in all patients, with the magnitude of this improvement being closely related to the baseline PRA. Thus, the overall hemodynamic response to CPT, which rapidly appears in the bloodstream following drug intake in patients with advanced CHF, is a function of the extent of baseline renin-angiotensin-aldosterone activity.
Clinical studies with captopril treatment of hypertensive patients
Acta physiologica Hungarica, 1988
Haemodynamic and humoral effects of captopril were studied in patients with essential and renovascular hypertension. Captopril decreased significantly both systolic and diastolic blood pressure and moderately, it reduced also the heart rate. On the basis of the haemodynamic effects our patients could be divided into two groups: in patients where the total peripheral resistance (TPR) exceeded 2000 dyn x sec x cm-5 during rest, captopril exerted its hypotensive effect by decreasing TPR. In patients in whom TPR was lower, the hypotensive action could be attributed to the reduction of cardiac output (CO). Captopril increased plasma renin activity, and decreased the activity of angiotensin converting enzyme (ACE) in the plasma. In acute study captopril did not influence plasma noradrenaline level but increased it during long-term administration. It did not affect dopamine or adrenaline levels. Captopril had no effect on plasma beta-endorphin concentration, moreover, the opiate antagonist...
Hypotensive and renal effects of Captopril
European Journal of Clinical Investigation, 1981
The effects of Captopril on blood pressure and renal function were evaluated in ten patients with different degrees of hypertension. In seven, blood pressure was reduced after 7 weeks of therapy; in three it remained practically unchanged. No correlation was found between the standing plasma renin activity before treatment and the hypotensive response. Plasma renin activity increased significantly from the median value of 5.4 (range 1-16.7) to 9.5 (range 2.6-19.8) ng ml-' h-' (P<O.O5) and urine aldosterone significantly fell from 13 (range 2.3-52.5) to 7.4 (range 1.614) pg 24 h-' (P<O.OI) during therapy. Renal plasma flow decreased from 534 (range 300-616) to 471 (range 333-606) ml min-I, but the difference was not significant, and glomerular filtration rate fell significantly form 122 (range 64-143) to 88 (range 71-1 16) ml min-' (P<O.O5). N o urinary excretion of alpha?-macroglobulin was observed during Captopril. 24 h proteinuria, albumin and transferrin clearance, alanine-amino transferase, gammaglutamyl transferase and alpha glucosidase excretion rate and malatedehydrogenase clearance remained unaltered throughout the treatment. This indicates that neither glomerular permeability nor renal tubular function were affected by the drug.
Hypertensive crisis treated with orally administered captopril
European Journal of Clinical Pharmacology, 1983
The value of the orally active converting enzyme inhibitor captopril in managing hypertensive crisis was tested in 9 untreated patients admitted to the emergency room, who were in need of rapid blood pressure reduction because of signs and symptoms of neurological and/or cardiac complications. During the 30 rain following administration of captopril 25mg the blood pressure decreased from 239/134 + 12/4 mmHg (mean + SEM) to 204/118 _+ 8/4mmHg (p<0.05). From that time on, captopril 200 to 300 rag/day was continued for 2 to 5 days. In 5 patients furosemide in a total dose of 40 to 160 mg i.v. or p. o. had also to be given in order to control the blood pressure. 12 and 24h after admission blood pressure averaged 140/93 and 139/86 mmHg respectively, in the patients treated with captopril alone, and 166/107 and 153/91 mmHg in those treated both with captopril and furosemide. The pronounced fall inblood pressure produced by blockade of the renin system was well tolerated and did not cause tachycardia. It appears, therefore, that captopril given alone or in association with a diuretic makes it possible to treat the hypertensive crisis without the need for monitoring in an intensive care unit.
Acta pharmacologica et toxicologica, 1981
Spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain (n = 40) were treated with captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) orally, dose 0.2 mg/ml in drinking water. The treatment was initiated early and later during the course of developing hypertension. Continuously treated rats did not develop hypertension. Rats receiving captopril for 12 weeks remained normotensive, whereas withdrawal of the drug resulted in hypertension. Captopril treatment was effective in the rats with established hypertension and decreased the blood pressures to nearly normal values. Serum angiotensin converting enzyme (ACE) activity rose 3-fold in captopril treated rats. ACE in lung plasma membranes increased during captopril treatment, indicating that captopril induced biosynthesis of pulmonary ACE. No qualitative differences were found in the ACE from treated and not treated animals. The dissociation of the antihypertensive effect of captopril and of increased ACE activity ...
Captopril kinetics in chronic congestive heart failure
Clinical Pharmacology and Therapeutics, 1982
We investigated the kinetics of 25 mg captopril by mouth in 12 patients with congestive heart failure and correlated them with the hormonal and hemodynamic changes associated with the drug. Observations were made after a single dose (25 mg orally), and after short-term therapy (25 mg t.i.d. for 3 days). Captopril kinetics were as previously reported in normal subjects, with the exception that time to maximum concentration (tmax) of free captopril was slightly higher and the half-life (t1/2) was slightly shorter than in normal subjects. Total captopril t1/2 was longer than normal, suggesting cumulation. Urinary excretion was slower than normal. Differences between captopril kinetics on days 1 and 5 were that the t m,. developed somewhat sooner, with a shorter t1/2 on day 5 and total captopril blood levels were higher on day 5 than on day 1. Urinary excretion was greater on day 5 than on day 1. Hemodynamic improvement after a single oral dose of captopril was significant and correlated with baseline plasma renin activity (PRA). The onset of converting-enzyme inhibition, as determined by PRA and hemodynamic improvement correlated with captopril blood levels.