Captopril pharmacokinetics

Richer C, Bah M, Cadilhac M, Thuillez C, Giudicelli JF. Cimetidine does not alter free unchanged captopril pharmacokinetics and biological effects in healthy volunteer. JPharmacol 0986) 17, 338-42. 

In conclusion, CPD represents a prodrug of captopril which seems to lengthen the pharmacokinetic half-life and extend the duration of action of captopril in humans. 

Captopril and enalapril are the standard examples of ACE-inhibitors, which have been used on a large scale for almost two decades. The differences between the two preparations are predominantly based on pharmacokinetic parameters. Enalapril is a prodrug, which is converted into its active compound enalaprilate after oral ingestion captopril is active as such. Enalapril can be given once daily, whereas... 

Captopril s pharmacokinetic parameters and dosing recommendations are set forth in Table 11-2. Peak concentrations of enalaprilat, the active metabolite of enalapril, occur 3-4 hours after dosing with enalapril. The half-life of enalaprilat is about 11 hours. Typical doses of enalapril are 10-20 mg once or twice daily. Lisinopril has a half-life of 12 hours. Doses of 10-80 mg once daily are effective in most patients. All of the ACE inhibitors except fosinopril and moexipril are eliminated primarily by the kidneys doses of these drugs should be reduced in patients with renal insufficiency. 

An important class of orally active ACE inhibitors, directed against the active site of ACE, is now extensively used. Captopril and enalapril are examples of the many potent ACE inhibitors that are available. These drugs differ in their structure and pharmacokinetics, but in clinical use, they are interchangeable. ACE inhibitors decrease systemic vascular resistance without increasing heart rate, and they promote natriuresis. As described in Chapters 11 and 13, they are effective in the treatment of hypertension, decrease morbidity and mortality in heart failure and left ventricular dysfunction after myocardial infarction, and delay the progression of diabetic nephropathy. 

Captopril s pharmacokinetic parameters and dosing recommendations are set forth in Table 11-1. 

Numerous other ACE inhibitors have been synthesized and evaluated since captopril was announced in 1977. As of 1996, 16 were in use worldwide (157), all of which are variations of the designs exemplified in Table IX. Reviews are available that describe dosage, pharmacokinetics, metabolism, and routes of elimination of many of them (111,156-159). 

Ohman, K.P. Kagedal, B. Larsson, R. Karlberg, B.E. Pharmacokinetics of captopril and its effects on blood pressure during acute and chronic administration and in relation to food intake. J. Cardiovasc. Pharmacol. 1985, 7 (Suppl. 1), 20-24. 

Miyakawa T, Shionoiri H, Takasaki I, Kobayashi K, Ishii M. The effect of captopril on pharmacokinetics of digoxin in patients with mild congestive heart failure. J Cardiovasc Pharmacol 1991 17(4) 576-80. 

First reports on the pharmacokinetics of captopril in man indicate that it is well absorbed orally and is excreted largely unchanged with a... 

Jankowski, A. Skorek, A. Krzysko, K. Zarzyxki, P.K. Ochocka, R.J. Lamparczyk, H. Captopril determination in blood and pharmacokinetics after single oral dose. J.Pharm.Biomed.Anal., 1995, 13, 655-660... 

D. Pharmacokinetics. (See also Table 11-59.) The volume of distribution (Vd) of ACE inhibitors is fairly small (eg, 0.7 L/kg for captopril). The parent drugs are rapidly converted to their active metabolites, with half-lives of 0.75-1.5 hours. The active metabolites have elimination half-lives of 5.9-35 hours. The AR blockers have half-lives of 5-24 hours losartan has an active metabolite. 

No significant pharmacokinetic changes were seen in 12 healthy subjects given allopurinol and captopril alone and in combination. ... 

An aluminium/magnesium hydroxide antacid reduced the bioavailability of captopril by 40%, but this did not seem to be clinically important The bioavailability of fosinopril was reduced by about one-third by Mylanta. An antacid did not affect ramipril pharmacokinetics. 

Duchin KL, McKinstry DN, Cohen AI, Migdalof BH. Pharmacokinetics of captopril in healthy subjects and in patients with cardiovascular diseases. ChnPharmacokinet ( 9ZZ) 14,241-59. 

Although food did not significantly affect the pharmacokinetics of a single 4-mg dose of perindopril, the AUC of its active metabolite perindoprilat was reduced by 44%. The blood pressure-lowering effects were not assessed, but it seems possible that they would not be affected (see captopril, above). Nevertheless, the UK manufacturer recommends that perindopril should be taken in the morning before a meal. ... 

Cimetidine did not appear to alter the pharmacokinetics or pharmacological effects of captopril or enalapril, or the pharmacokinetics of fosinopril or quinapril in studies in healthy subjects. The manufacturers of cilazapril say that no clinically significant interaction occurred with H2-receptor antagonists (not specifically named) and the manufacturers of moexipril, " ramipril, and trandolapril say that no important pharmacokinetic interaction occurred with cimetidine. The manufacturers of spirapril briefly note in a review that cimetidine did not alter the plasma concentrations of spirapril or its active metabolite spiraprilat. None of these pairs of drugs appears to interact to a clinically relevant extent, and no special precautions appear to be necessary. 

Moracizine causes some moderate alterations in the pharmacokinetics of free captopril, but these are unlikely to be clinically important. 

In a pharmacokinetic study, 19 healthy subjects were given moracizine 250 mg or captopril 50 mg, both every 8 hours, either alone or together, for 22 doses. When taken together the pharmacokineties of the moracizine and total captopril remained unchanged, but the maximum blood levels of the free captopril and its AUC decreased by 32% and 14%, respectively. The half-life of the free captopril was reduced by 44%. These modest changes are unlikely to be clinically relevant. 

Pieniaszek HJ, Shum L, Widner P, Gamer DM, Benedek IH. Pharmacokinetic interaction of moricizine and captopril in healthy volunteers, j Clin Pharmacol (1993) 33,1005. 

However, the manufaeturer has found no evidenee of an assoeiation between orlistat and hypertension. In elinieal studies, orlistat use was asso-eiated with a small reduetion in blood pressure eompaied with placebo, which was as a result of weight reduction. Moreover, the incidence of hypertension of new onset and hypertensive crisis did not differ between orlistat and placebo (1.2% versus 1.3%, and 0% versus 0.1%, respectively). In studies in healthy subjects, orlistat had no effect on steady-state losar-tan pharmacokinetics, and no clinically significant effect on the pharmacokinetics of single-dose captopril, atenolol, furosemide or nifedipine. ... 

The combination of captopril or other ACE inhibitors and procainamide possibly increases the risk of lencopenia. No pharmacokinetic interaction occurs between captopril and procainamide. 

A study in 12 healthy subjects given digitoxin 70 micrograms daily for up to 58 days found no evidence that the addition of captopril 25 mg daily had a relevant effect on the pharmacokinetics of digitoxin, or its effects on the heart. ... 

Rossi GP, Semplicini A, Boi ovi S, Mozzato MG, Paleari CD, Pessina AC. Effect of acute captopril administration cn digoxin pharmacokinetics in normal subjects. Curr Ther Res (1989) 46,439. ... 

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