Pharmacokinetics and Pharmacodynamics of Captopril in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

Fujimura, Akio; Kajiyama, Hiroyuki; Ebihara, Akio; Iwashita, Koichi; Nomura, Yoshio; Kawahara, Yukinori

doi:10.1159/000184014

Cited by 20 publications

(4 citation statements)

References 14 publications

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“…With initiation of dialysis 1 hour after oral administration of captopril, approximately 35% of an oral dose was recovered in the dialysate following a standard 4-hour dialysis procedure (Duchin et al 1984). Captopril has also been shown to be removed by peritoneal dialysis (Fujimara et al 1986). …”

Section: Chronic Renal Failurementioning

confidence: 99%

Pharmacokinetics of Captopril in Healthy Subjects and in Patients with Cardiovascular Diseases

Duchin

McKinstry

Cohen

et al. 1988

Clinical Pharmacokinetics

130

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Captopril, the first orally active inhibitor of angiotensin-converting enzyme, is used widely in the treatment of hypertension and congestive heart failure. The pharmacokinetics of this agent have been studied extensively in healthy subjects and in patients with hypertension, congestive heart failure, and chronic renal failure. Captopril contains a sulphydryl group and binds readily to albumin and other plasma proteins. The drug also forms mixed disulphides with endogenous thiol-containing compounds (cysteine, glutathione), as well as the disulphide dimer of the parent compound. These components in blood and urine are measured collectively as total captopril. Because of the reversibility of the formation of these inactive disulphides, total captopril may serve as a reservoir of the pharmacologically active moiety, and thus contribute to a duration of action longer than that predicted by blood concentrations of unchanged captopril. To measure free or unchanged captopril concentrations, a chemical stabiliser must be added to the biological samples to prevent the formation of captopril disulphides ex vivo. In healthy subjects given captopril intravenously, the body clearance of captopril and steady-state volume of distribution were about 0.7 L/h/kg and 0.8 L/kg, respectively. The elimination half-life of unchanged captopril was approximately 2 hours. The primary route of elimination of captopril is the kidney. The renal clearance of unchanged captopril exceeds the glomerular filtration rate, due to active tubular secretion of the drug. In healthy subjects, about 70 to 75% of an oral dose is absorbed and the bioavailability of captopril is approximately 65%. Peak blood concentrations are reached about 45 to 60 minutes after oral administration. The bioavailability of captopril is not altered by age or concomitant medications including diuretics, procainamide, allopurinol, cimetidine or digoxin. However, the co-administration of food or antacids, or probenecid with captopril has been shown to diminish the bioavailability of the latter and decrease its clearance, respectively. The decreased bioavailability of captopril when taken with meals does not significantly alter clinical responses to the drug. Over a wide range of oral (10 to 150 mg) and intravenous doses (2.5 to 10 mg) captopril had linear kinetics in healthy volunteers. In healthy subjects with normal renal function and patients with congestive heart failure given captopril 3 times daily, blood concentrations of total captopril accumulated, whereas those of unchanged captopril did not. Severe renal insufficiency was associated with an accumulation of both unchanged and total captopril.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Chronic Renal Failurementioning

confidence: 99%

Pharmacokinetics of Captopril in Healthy Subjects and in Patients with Cardiovascular Diseases

Duchin

McKinstry

Cohen

et al. 1988

Clinical Pharmacokinetics

130

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“…The tmax reported in CAPD patients after 20 mg was 5.4 (2.5) (SD) h [4] and 4.5 (2.5) (SD) h in chronic HD patients [3]. For comparison, the tmax of captopril was about 1 h in healthy subjects, and it has been reported not to be changed (0.7-2 h) in HD [5] and CAPD (1.1 h) patients [6]. By contrast, tmax of enalaprilat is 3-4 h in healthy subjects and has been reported to be prolonged 8-fold up to 24 h in HD patients [7].…”

Section: Discussionmentioning

confidence: 94%

Pharmacokinetics and pharmacodynamics of quinaprilat after low dose quinapril in patients with terminal renal failure

Wolter

Fritschka

1993

Eur J Clin Pharmacol

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The pharmacokinetics and pharmacodynamics of the ACE inhibitor quinaprilat have been studied in six chronic haemodialysis (HD) patients and in six patients undergoing continuous ambulatory peritoneal dialysis (CAPD) after a single oral dose of 2.5 mg quinapril. Mean tmax and Cmax values (SEM) for quinaprilat in interdialytic HD patients were 4.0 (0) h and 84 (8.4) ng.ml-1 respectively, and they did not differ significantly from those in CAPD patients (4.7 (0.7) h and 64 (5.7) ng.ml-1). Elimination half lives were 30 (10.1) h (HD) and 34 (7.3) h (CAPD). Cmax, tmax, t1/2, and AUC were increased and CL was decreased compared to data reported previously after giving 2.5 mg to healthy subjects. Peritoneal clearance was calculated as 0.1 (0.1) ml.min-1, thus less than 0.5% of the dose were removed within 24 h by CAPD. ACE activity was suppressed by more than 93% between 4 and 24 h postdose (P < 0.001). It decreased in both groups with increasing plasma quinaprilat levels. Angiotensin II concentration compared to baseline was significantly decreased at 4 hours (-30.4 +/- 10%) and 24 h (-30 +/- 9.9%) (P < 0.05, n = 11), while active plasma renin concentration was still significantly increased at 48 h postdose (+ 60.2 +/- 14.5%, P < 0.01). Mean arterial pressure 24 h postdose was significantly (P < 0.05) decreased in HD (-12 mmHg) and CAPD patients (-20 mm Hg). Only two patients reported unwanted effects (fatigue, dizziness, nausea, and weakness). In conclusion, due to its long lasting effect on ACE activity and on blood pressure in terminal renal failure a starting dose of quinapril 2.5 mg o.d. may be used in hypertensive HD and CAPD patients.

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“…It has a short half-life in human plasma, ranging from 1.6 to 1.9 hours. About 70% of the oral dose is absorbed and has an absolute bioavailability of 60% in a healthy fasting human individual (Fujimura et al, 1986;Duchin et al, 1988). Captopril demonstrated fast absorption in a single-dose pharmacokinetic trial in which 25mg was administered to 12 volunteers.…”

Section: Figure 1 Structure Of Captoprilmentioning

confidence: 99%

Titrimetric and thin layer chromatographic fingerprint analysis of captopril solid dosage form – an Angiotensin- Converting Enzyme Inhibitor

J Bunu,

Kela−Eke,

U Ebeshi

2024

Drug Dicov

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Pharmacokinetics and Pharmacodynamics of Captopril in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

Cited by 20 publications

References 14 publications

Pharmacokinetics of Captopril in Healthy Subjects and in Patients with Cardiovascular Diseases

Pharmacokinetics of Captopril in Healthy Subjects and in Patients with Cardiovascular Diseases

Pharmacokinetics and pharmacodynamics of quinaprilat after low dose quinapril in patients with terminal renal failure

Titrimetric and thin layer chromatographic fingerprint analysis of captopril solid dosage form – an Angiotensin- Converting Enzyme Inhibitor

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