The effects of captopril on serum digoxin and urinary urea and digoxin clearances in patients with congestive heart failure

Cleland, John G.F.; Dargie, Henry J.; Pettigrew, A; Gillen, G.; Robertson, J. I. S.

doi:10.1016/0002-8703(86)90690-3

Cited by 47 publications

(11 citation statements)

References 27 publications

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“…Digoxin concentrations are increased when it is combined with some antiarrhythmics (quinidine and amiodarone), calcium channel blockers, particularly verapamil, and to a lesser extent with nifedipine and diltiazem, and with the angiotensin converting enzyme inhibitor captopril (Cleland et al 1986). Digoxin, for instance, interacts with a number of drugs and it is therefore necessary to reduce the dose to avoid toxicity.…”

Section: Resultsmentioning

confidence: 99%

Clinical Pharmacokinetics in Heart Failure

Fv¹,

Dickstein²

1988

Clinical Pharmacokinetics

117

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Pharmacokinetics is the study of the effect that the body has on drug absorption, distribution, metabolism and excretion. The pharmacokinetics of a specific drug are assessed by the volume of distribution, bioavailability, clearance and elimination half-life. Elimination half-life is directly related to the volume of distribution and inversely related to clearance. Any 1 or more of these parameters may be altered by physiological changes such as ageing, or disease states such as congestive heart failure. Congestive heart failure is associated with hypoperfusion to various organs including the sites of drug clearance, i.e. the liver and kidneys. It also leads to organ congestion as seen in the liver and gut. The main changes in drug pharmacokinetics seen in congestive heart failure are a reduction in the volume of distribution and impairment of clearance. The change in elimination half-life consequently depends on whether both clearance and the apparent volume of distribution change, and the extent of that change. Pharmacokinetic changes are not always predictable in congestive heart failure, but it seems that the net effect of reduction in the volume of distribution and impairment of clearance is that plasma concentrations of drugs are usually higher in patients with congestive heart failure than in healthy subjects. The changes in pharmacokinetics assume importance only in the case of drugs with a narrow therapeutic ratio (e.g. digoxin) and some of the antiarrhythmics such as lignocaine (lidocaine), procainamide and disopyramide. This necessitates reduction in both the loading and maintenance doses. Prolongation of the elimination half-life leads to delay in reaching steady-state, and therefore dose increments must be made more gradually. Plasma concentration measurements of the drugs concerned are a good guide to therapy and help to avoid toxicity. Pharmacokinetic changes are of less importance in the case of drugs with immediate clinical response, e.g. diuretics and intravenous vasodilators such as nitrates and phosphodiesterase inhibitors. The dose in the latter group can be titrated to the desired effect. Not all adverse reactions to drugs that may occur in heart failure are the result of alterations in pharmacokinetics; rather, some may be due to important drug interactions. An interaction may occur directly e.g. reduction of renal clearance of digoxin by captopril and quinidine; or indirectly, e.g. through diuretic-induced hypokalaemia, which exacerbate arrhythmias associated with digoxin and antiarrhythmics such as quinidine and procainamide.

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Section: Resultsmentioning

confidence: 99%

Clinical Pharmacokinetics in Heart Failure

Fv¹,

Dickstein²

1988

Clinical Pharmacokinetics

117

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“…Therefore, inhibition of intestinal P-glycoprotein is the reason for higher AUC-values only if changes of renal clearance are excluded by the interaction study. It is also important to recognize that many drugs given concomitantly with digoxin may influence renal blood flow and renal digoxin clearance independent of whether they interact with P-glycoprotein as suggested for nitropusside, hydralazine or captopril (Cleland et al 1986;Cogan et al 1981;Mujais et al 1984). …”

Section: Limitations Of Digoxinmentioning

confidence: 99%

In Vivo Probes of Drug Transport: Commonly Used Probe Drugs to Assess Function of Intestinal P-glycoprotein (ABCB1) in Humans

Oswald

Terhaag

Siegmund

2010

Handbook of Experimental Pharmacology

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Intestinal P-glycoprotein (P-gp, ABCB1) may significantly influence drug absorption and elimination. Its expression and function is highly variable, regio-selective and influenced by genetic polymorphisms, drug interactions and intestinal diseases. An in vivo probe drug for intestinal P-gp should a registered, safe and well tolerated nonmetabolized selective substrate with low protein binding for which P-gp is rate-limiting during absorption. Other P-gp dependent processes should be of minor influence. The mechanism(s) and kinetics of intestinal uptake must be identified and quantified. Moreover, the release properties of the dosage form should be known. So far, the cardiac glycoside digoxin and the ß₁-selective blocker talinolol have been used in mechanistic clinical studies, because they meet most of these criteria. Digoxin and talinolol are suitable in vivo probe drugs for intestinal P-gp under the precondition, that they are used as tools in carefully designed pharmacokinetic studies with adequate biometrically planning of the sample size and that several limitations are considered in interpreting and discussion of the study results.

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“…A variety of mechanisms can contribute to drug interactions with digoxin, including alterations in renal and nonrenal clearance, absorption and distribution volume [3][4][5][6]. For example, captopril increases serum digoxin by about 25% and the mechanism involved appeared to be a reduction of renal clearance of digoxin [11]. In contrast, neither ramipril nor lisinopril altered digoxin levels in volunteers [12,13].…”

Section: Discussionmentioning

confidence: 99%

Effect of multiple doses of losartan on the pharmacokinetics of single doses of digoxin in healthy volunteers.

Smet¹,

Schoors²,

Meyer³

et al. 1995

Brit J Clinical Pharma

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1 Losartan (DuP 753, MK-954) is a novel, potent and highly selective AT1angiotensin II receptor antagonist. The effect of multiple oral doses of losartan on digoxin pharmacokinetics was evaluated in healthy male subjects. 2 In a double-blind and randomized fashion, subjects received 50 mg losartan or placebo once daily for 15 days in each period. At least 7 days elapsed between the two treatment periods. On days 4 and 11 of each period, subjects also received a single 0.5 mg dose of digoxin intravenously and orally respectively. 3 Eleven of 13 subjects completed the study. Side effects were mild and transient (12 out of 13 subjects reported at least one adverse experience). During the study, no laboratory abnormalities were noted. 4 Multiple oral doses of losartan (50 mg

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The effects of captopril on serum digoxin and urinary urea and digoxin clearances in patients with congestive heart failure

Cited by 47 publications

References 27 publications

Clinical Pharmacokinetics in Heart Failure

Clinical Pharmacokinetics in Heart Failure

In Vivo Probes of Drug Transport: Commonly Used Probe Drugs to Assess Function of Intestinal P-glycoprotein (ABCB1) in Humans

Effect of multiple doses of losartan on the pharmacokinetics of single doses of digoxin in healthy volunteers.

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