Myocardial and Skeletal Muscle Concentrations of Digoxin in Patients on Long-term Therapy

Coltart, J; Howard, M. R.; Chamberlain, Douglas

doi:10.1136/bmj.2.5809.318

Cited by 93 publications

(28 citation statements)

References 9 publications

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“…This is contradictory to other animal and human studies (4,5,12), and our own observa tions (unpublished data). Perhaps data reported here are unique to mice, or as steady-state drug concentrations are approached, the concentra tions in other tissues, such as the heart, become greater than those in skeletal muscle.…”

Section: Methodscontrasting

confidence: 56%

Age-Associated Changes in Tissue Distribution and Uptake of <sup>3</sup>H-Digoxin in Mice and Guinea Pigs

Kroening¹,

Weintraub²

1980

Pharmacology

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The influence of age on tissue distribution of digoxin in mice and guinea pigs and uptake by mouse heart slices was investigated. 4 h after a single dose of ³H-digoxin, tissue:plasma ratios were significantly greater in very young animals and declined with increasing age. A similar relationship was apparent for packed red blood cell:plasma concentration ratios in mice. Uptake of ³H-digoxin by heart tissue slices was also higher for 21-day-old mice than 200-day-old mice. These data seem to correlate with the larger volume of distribution of digoxin observed in the young. Tissue digoxin relative to plasma concentration seems higher in the young, although they appear less sensitive to the effects of cardiac glycosides.

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Section: Methodscontrasting

confidence: 56%

Age-Associated Changes in Tissue Distribution and Uptake of <sup>3</sup>H-Digoxin in Mice and Guinea Pigs

Kroening¹,

Weintraub²

1980

Pharmacology

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“…Another investigated drug is digoxin whose therapeutic activity is likely to correlate with the concentration at the active sites in the tissue rather than with the plasma concentration [105]. Great disparity was shown between those two concentrations as digoxin binds to cardiac tissue to a great extent.…”

Section: Cardiac Pharmaceutical Agentsmentioning

confidence: 99%

“…to sodium-potassium activated membrane adenosine triphosphatase. Thus, the total myocardial concentration may be of limited value [105,109]. It is even more complicated with regard to digitoxin which has few metabolites.…”

Section: Cardiac Pharmaceutical Agentsmentioning

confidence: 99%

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Tylutki

Polak

2015

Biopharm & Drug Disp

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ABSTRACT:Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart.

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“…4 Amiodarone may displace tissue-bound glycoside or interfere with digoxin excretion, but the mechanism has not yet been investigated in detail. High plasma concentrations ofdigoxin without commensurate increases in myocardial concentrations would be expected to cause neurotoxicity rather than direct cardiac toxicity; but heart rhythm may be influenced by both mechanisms.5…”

Section: Commentmentioning

confidence: 99%

Amiodarone increases plasma digoxin concentrations.

Moysey¹,

Jaggarao²,

Grundy³

et al. 1981

BMJ

185

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Myocardial and Skeletal Muscle Concentrations of Digoxin in Patients on Long-term Therapy

Cited by 93 publications

References 9 publications

Age-Associated Changes in Tissue Distribution and Uptake of <sup>3</sup>H-Digoxin in Mice and Guinea Pigs

Age-Associated Changes in Tissue Distribution and Uptake of <sup>3</sup>H-Digoxin in Mice and Guinea Pigs

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Amiodarone increases plasma digoxin concentrations.

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