Digoxin Concentrations in the Serum and Myocardium of Digitalised Patients*

Carroll, Peter R.; Gelbart, Alex; O'rourke, M. F.; Shortus, Juliana

doi:10.1111/j.1445-5994.1973.tb03113.x

Cited by 29 publications

(5 citation statements)

References 6 publications

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“…The majority of these have suggested that myocardial digoxin concentration is approximately 70 times higher than plasma concentration at steadystate (Carroll et al 1973;Carruthers et al 1975;Hartel et al 1976), although atrial drug concentrations may be somewhat lower than ventricular. A possible technical problem is raised by the use of conventional, direct radioimmunoassays which also detect digoxin metabolites.…”

Section: Uptake Of Digoxinmentioning

confidence: 97%

Myocardial Uptake of Drugs and Clinical Effects

Horowitz

Powell

1986

Clinical Pharmacokinetics

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The process of uptake of cardioactive drugs into the myocardium is a major determinant of the efficacy and potential toxicity of such agents. Evaluation of responses to anti-arrhythmic and positive inotropic agents is best performed with reference to their concentration in the myocardium, and the potential toxicity of drugs such as tricyclic antidepressants and anthracycline antineoplastics is likely to be related to peak myocardial drug concentrations. Although it has been appreciated for many years that even during long term drug administration the myocardial drug content may not be readily predictable on the basis of estimation of plasma drug concentrations, methodology for direct assessment of myocardial drug content has remained limited. The results of in vitro experiments, utilising tissue culture preparations of myocardial cells or isolated atria, have shed some light on the role of local factors as determinants of myocardial drug uptake. For many agents, attainment of maximal cardiac drug content in vitro is a very slow process (taking up to 3 hours), although maximal inotropic and electrophysiological effects may occur more rapidly. The prolonged time course of drug washout from these preparations also reflects their extensive and slow intracellular accumulation. Mechanical activity of the myocardium appears to accelerate drug uptake, particularly for otherwise slowly equilibrating agents, but the major determinant of the extent of drug uptake into isolated myocardial preparations is lipophilicity, perhaps reflecting the passage of drugs through the sarcolemma. In intact animals, assessment of myocardial drug content after acute drug administration has been performed utilising serial myocardial biopsy or sacrifice of animals. Studies in open-chested dogs suggest that acute accumulation of agents may be most closely predicted from the second compartment of a 3-compartment pharmacokinetic model, and that there is a variable correlation between changes in plasma and myocardial drug concentrations. For example, bretylium concentrations within the myocardium continue to increase for up to 6 hours after drug administration. Factors which may influence drug uptake into the myocardium in intact animals include ischaemia, which usually results in a delay in both drug uptake and subsequent clearance. This change can also be inferred from the time course of onset of antiarrhythmic drug effects in some models of myocardial ischaemia. Anoxia may also inhibit myocardial drug uptake.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Uptake Of Digoxinmentioning

confidence: 97%

Myocardial Uptake of Drugs and Clinical Effects

Horowitz

Powell

1986

Clinical Pharmacokinetics

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“…However, direct comparisons between different series are difficult because of the variability in, or lack of information about, digoxin dosage regimens and intervals between discontinuation of therapy and sampling blood and tissue digoxin levels. Thus, some authors have neglected to state the usual daily dose and drug discontinuation interval before surgery (Coltart et al,I972), others have stopped digoxin treatment at the same time in patients receiving different doses (Binnion et al,I969) or have brought together patients with both different dosage regimens and different intervals between drug discontinuation and operation (Carroll et al, 1973). In these studies, the results were analysed in total groups.…”

Section: Discussionmentioning

confidence: 99%

“…Initially Doherty, Received 22 July 1974. Perkins, and Flanigan (I967) suggested that a relatively constant ratio existed between the two, but subsequent investigations have not supported this (Binnion et al,I969;Coltart,Howard,and Chamberlain,I972;Carroll et al,I973) and wide variations in myocardial tissue digoxin concentrations have been reported. Carroll et al (1973) have recently suggested that there is no difference between the atrial and ventricular concentrations of the drug in humans, but this is at variance with results obtained from dogs (Deutscher,Harrison,and Goldman,I972) and from human necropsy studies after administering radioactive digitoxin (Okita et al, 1955).…”

mentioning

confidence: 90%

Plasma and tissue digoxin concentrations in patients undergoing cardiopulmonary bypass.

Carruthers¹,

Cleland²,

Kelly³

et al. 1975

Heart

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Plasma myocardial, and skeletal muscle digoxin concentrations were measured in 32 patients undergoing cardiopulmonary bypass who were on long-term treatment with digoxin. The patients were divided into 4 groups according to the daily digoxin dose and the interval between discontinuation of the drug and operation. Before bypass, the mean digoxin concentrations were 1.58 nmol/l (1.24 ng/ml) in plasma 65.2 nmol/kg (50.9 ng/g) in the atria, 121.4 nmol/kg (94.98 ng/g) in 11 papillary muscles, and 16.6 nmol/kg (13.0 ng/g) in skeletal muscle. Mean atrial digoxin concentrations were significantly lower tham mean papillary muscle concentrations in 11 patients. Ratios of plasma of myocardial or skeletal muscle digoxin concentrations were very variable. Generally digoxin concentrations were higher in patients on the larger digoxin dose and with the shorter discontinuation time before surgery. These differences attained significance only with plasma digoxin concentrations. There was a slight fall in plasma digoxin concentration during cardiopulmonary bypass but no significant differences were observed between plasma, atrial, or skeletal muscle digoxin concentrations before and at the end of bypass. No clear relation was seen between plasma or atrial digoxin concentrations and postoperative cardiotoxicity. Stopping digoxin 48 hours before operation appeared to account for pre- or post-bypass plasma digoxin concentrations of less than 1.0 nmol/l (0.8 ng/ml) in most of the instances encountered, whereas the 3 patients who developed pulsus bigeminus postoperatively had received 0.5 mg digoxin only 24 hours before operation.

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“…The metabolie patterns of both eardioaetive and inaetive, eonju-395 20.00 ± 3. 25 21.75 ± 3.84 (10) (6) gated metabolites in myoeardial autopsy sam-pIes from patients on maintenanee treatment with digitoxin were also investigated.…”

mentioning

confidence: 99%

Studies on digitalis; X. Digitoxin metabolites in human myocardium and relationship between myocardial and serum concentrations of digitoxin in patients on maintenance treatment

Storstein

1977

Clin Pharma and Therapeutics

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The levels of digitoxin and cardioactive metabolites were measured in 42 atrial biopsies with a 86Rb method modified for analysis of myocardial samples. The mean value was 91.0 ng/gm wet weight (SD 54.4). Myocardial and serum concentrations were compared in 23 patients; there was no significant correlation. The ratio of total drug concentration in myocardium and serum ranged from 1 to 38 with a mean value of 5.4. Calculated from the free drug concentrations, the mean myocardial serum ratio was 200, which reflects the high affinity of digitoxin and cardioactive metabolites to the myocardium. The metabolic pattern of cardioactive and inactive metabolites (conjugates with glucuronic and sulfuric acid) was studied in autopsy samples from left ventricular myocardium from 7 patients. Significant differences between the myocardial and serum patterns of cardioactive and inactive metabolites were demonstrated. The myocardium contained less unchanged digitoxin (25.7%) and more hydrolyzed (55.4%) and conjugated (54.1%) metabolites than serum (57.6%, 31.0%, and 33.1%, respectively). Hydroxylated metabolites in myocardium (15.8%) were not significantly changed compared to serum (10.0%).

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Digoxin Concentrations in the Serum and Myocardium of Digitalised Patients*

Abstract: In an attempt to evaluate the 1 serum digoxin concentration as a guide to digitalis treatment, serum and myocardial concentrations were measured in 27 patients undergoing cardiac surgery.

Cited by 29 publications

References 6 publications

Myocardial Uptake of Drugs and Clinical Effects

Myocardial Uptake of Drugs and Clinical Effects

Plasma and tissue digoxin concentrations in patients undergoing cardiopulmonary bypass.

Studies on digitalis; X. Digitoxin metabolites in human myocardium and relationship between myocardial and serum concentrations of digitoxin in patients on maintenance treatment

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