Interpretation of the Serum Digoxin Concentration

Weintraub, Michael

doi:10.2165/00003088-197702030-00005

Cited by 20 publications

(13 citation statements)

References 46 publications

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“…In contrast, these results in healthy volunteers do not rule out the possibility of an interaction under conditions in which digoxin pharmacokinetics would be modified such as oedema of decompensated heart failure, organic or functional renal failure, or the concomitant prescription of drugs which modify digoxin pharmacokinetics (some antiarrhythmics, in particular quinidines, and calcium antagonists) (Doherty & Perkins, 1962;Weintraub, 1983).…”

Section: Discussionmentioning

confidence: 85%

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Pharmacodynamic without pharmacokinetic interaction between cicloprolol, a partial beta 1‐adrenoceptor agonist, and digoxin in healthy subjects.

Weber

Kahan

Pinquier

et al. 1990

Brit J Clinical Pharma

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1 Cicloprolol is a partial P,B-adrenoceptor agonist considered for the treatment of patients with coronary artery disease and impaired left ventricular function. In such patients, digoxin remains in widespread use. 2 We assessed the pharmacokinetic and pharmacodynamic interaction between oral cicloprolol 50 mg day-' and oral digoxin 0.25 mg day-' in 10 healthy male volunteers, using a double-blind, randomised protocol, during three 8 day periods. Digoxin was given alone during the first period to reach steady state; then digoxin was given with cicloprolol or placebo during the second and third periods, according to a cross-over design. 3 No significant adverse effects were observed. 4 The pharmacokinetics of digoxin were not different significantly at the end of the placebo-digoxin and cicloprolol-digoxin periods. 5 A significant increase in minimum heart rate and mean nocturnal heart rate, assessed by 24 h Holter recordings, was observed at the end of the cicloprolol-digoxin period as compared with the placebo-digoxin period (means ± s. e. mean, 57.1 ± 3.2 beats min' vs 52.2 ± 3.1 beats min-1, P < 0.01; and 65.6 ± 3.8 beats min-1 vs 59.9 ± 3.9 beats min-I P < 0.01, respectively). 6 A significant increase in left ventricular ejection fraction and shortening fraction, assessed by echocardiography, was noted at the end of the cicloprolol-digoxin period as compared with the placebo-digoxin period (means ± s.e. mean, 66.4 ± 1.4% vs 61.3 + 1.2%, P < 0.05; and 37.0 ± 1.1% vs 33.3 ± 0.9%, P < 0.05, respectively). 7 These results demonstrate that cicloprolol does not modify digoxin pharmacokinetics in healthy male volunteers; they also show that the coadministration of the two drugs induces a positive inotropic effect and is well tolerated in these subjects.

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Section: Discussionmentioning

confidence: 85%

“…The radioimmunoassay of digoxin was not affected by the presence of cicloprolol. The percentage recovery of digoxin was 86% with a precision and reproducibility that was normal for a radioimmunoassay (Smith et al, 1969;Weintraub, 1983).…”

Section: Pharmacokinetic Studymentioning

confidence: 80%

Pharmacodynamic without pharmacokinetic interaction between cicloprolol, a partial beta 1‐adrenoceptor agonist, and digoxin in healthy subjects.

Weber

Kahan

Pinquier

et al. 1990

Brit J Clinical Pharma

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“…Advanced heart disease, acute and chronic pulmonary disease and impaired atrioventricular conduction all increase the risk of cardiotoxicity (Beller et aI., 1971;Fogelman et aI., 1971;Smith and Haber, 1970) and the need for regular reassessment. See further, recent reviews in the journal (Greenblatt et aI., 1976;Iisalo, 1977;Rane and Wilson, 1976;Weintraub, 1977;Wettrell and Andersson, 1977).…”

Section: Follow-up Of Patients Receiving Maintenance Digoxinmentioning

confidence: 99%

Prediction of Digoxin Dose Requirements

Dobbs

Mawer

1977

Clinical Pharmacokinetics

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Succes~ful withdrawal of digoxin in small highly selected groups of patients and in larger groups, in which many patients had no cardiac lesion, have led to speculation as to the value of maintenance digoxin following an episode of heart failure. Recent experience in general medical outpatients receiving'maintenance digoxin, and also in many cases potent diuretics, suggests that such doubts are largely misplaced. D(fferences in bioavailability between formulations have hindered the prediction of dose requirements. Standardisation of dissolution rate has reduced this contribution to the measured variation in individual absorption, but substantial variation remains which is probably due to individual differences in gastrointestinal function.The best criterion by which to judge the appropriateness of a prescription would be the clinical response of the patient. Nevertheless, guidelines are required for initial treatment and even for long term treatment of those patients in whom there is no convenient indicator of therapeutic response. In both situations, renal function, measured by creatinine clearance, has been the best gUide to the dose schedule required to achieve the desired mean steady state serum digoxin concentration. In adult patients with normal or only slightly impaired renal function, and normal atrio-ventricular conduction, the most practical procedure may be to start all patients on the same dose schedule.Symptoms of toxicity can occur at mean serum concentrations within the published therapeutic range. In these circumstances, reduction of the dose by small steps may abolish toxicity without loss of therapeutic response. Failure to reduce the dose encourages non-compliance. Further reduction during fott'ow-up may be necessary because of deterioration of renal function or progression of cardiac disease.Prescription of digoxin is a controversial matter. urged by recent editorials (British Medical Journal, 1975; Lancet, 1976). Attempts to increase the consistency of absorption of digoxin between subjects by using tablets of very high dissolution rate, fluid-fJ11ed capsules and more fat soluble, semisynthetic derivatives of digoxin are based on the assumption that the problem lies in the bioavailability of the drug, rather than the absorptive capacity of individual patients.Disagreement exists as to the indications for the drug and the best formulation. Although there is concern that many patients are prescribed inappropriate doses, prescribing aids are not generally used. The value of digoxin treatment after an episode of heart failure has been disputed, and reduction of the number of patients needlessly exposed to the drug

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“…In animal studies, digoxin distribution in the myocardium has been shown to be affected in different ways by a variety of pathological factors, including ischaemia or changes in blood flow to various portions of the heart (Beller et aI., 1972;Hopkins et aI., 1973), electrolyte disturbances (Binnion and Morgan, 1971;Harrison and Wakim, 1969;Marcus et aI., 1969), combined hypoxia and hypercapnia (du Souich et aI., 1985a), but not isolated hypoxia (du Souich et aI., 1985b). The distribution of digoxin appears to be altered also in thyroid disease (Aronson, 1980b) and in renal failure (Aronson and Orahame-Smith, 1976;Weintraub, 1977). Impairment in renal function, for example, is associated with a reduced volume of distribution and lower tissue binding -a strong positive correlation between myocardium/serum digoxin concentration ratios and estimated premorbid creatinine clearance has 507 been described in digoxin-treated patients studied at autopsy (Jusko and Weintraub, 1974).…”

Section: Disease-induced Alteration In Tissue Distributionmentioning

confidence: 99%

Interpretation of Drug Levels in Acute and Chronic Disease States

Perucca

Grimaldi

Crema

1985

Clinical Pharmacokinetics

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Serum drug concentration monitoring can be an invaluable aid to patient management, particularly in certain pathological conditions when individualisation of dosage is particularly critical. To be clinically useful, however, drug levels must be interpreted in the context of all factors that could influence the correlation between the concentration of the drug in plasma and the intensity of action. Several such factors may be operating in acute and chronic disease states. For example, a number of pathological conditions are associated with marked changes in the fraction of free, pharmacologically active drug in plasma and this will result in disruption of the normal relationship between total serum drug level and effect, as seen for phenytoin in uraemia. An altered response to a given serum drug level in disease states may also be caused by changes in tissue distribution, by abnormal accumulation of pharmacologically active metabolites in plasma or by changes in end-organ responsiveness. The latter are best illustrated by the altered sensitivity to digoxin in patients with various conditions, including hypokalaemia and thyroid disease. In addition to the factors listed above, consideration should also be given to potential interactions with concomitantly used drugs and to the possibility of analytical errors, especially in view of the evidence that the performance of otherwise reliable drug assays may be grossly impaired in certain diseases (e.g. uraemia), due to abnormal plasma composition and/or accumulation of interfering metabolites. In view of these complexities, a correct interpretation of serum drug levels requires a good knowledge of clinical pharmacology and a close collaboration between physician and laboratory. In any case, serum drug concentrations, like other laboratory tests, are not a substitute for careful patient observation, and any decision about drug treatment should be primarily based upon evaluation of the clinical state and, whenever possible, direct measurement of drug effects.

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Interpretation of the Serum Digoxin Concentration

Cited by 20 publications

References 46 publications

Pharmacodynamic without pharmacokinetic interaction between cicloprolol, a partial beta 1‐adrenoceptor agonist, and digoxin in healthy subjects.

Pharmacodynamic without pharmacokinetic interaction between cicloprolol, a partial beta 1‐adrenoceptor agonist, and digoxin in healthy subjects.

Prediction of Digoxin Dose Requirements

Interpretation of Drug Levels in Acute and Chronic Disease States

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