Tissue Concentrations of Digoxin in an Autopsy Material

Abstract

The tissue concentrations of digoxin were measured in 13 cadavers who before death had been on the maintenance digoxin therapy. Tissue samples were taken from 5 different parts of the heart, from skeletal muscle, liver and kidney. Digoxin was extracted by dichlormethane and measured by radioimmunoassay. Whole blood digoxin was measured by the same method. The appropriate recovery studies showed good extraction. The highest heart digoxin concentration was found in the septa1 muscle (mean 132 5 S . D . 65 nglg) and the lowest in the left auricle (43 & 26 ng/g). The heart concentrations were in good correlation with the whole blood concentrationthe best correlation was found with the ventricular muscle (r = 0.86). The skeletal muscle concentration was about 15 % of the heart concentration (20 t 13 ng/g) and the correlation with the whole blood was poorer (r = 0.54). The kidney concentration (123 5 65 nglg) was approximately the same as that of the heart and the liver concentration was 68 -I 51 nglg. The results indicate a linear correlation between blood and heart.

Inflammasome inhibition blocks cardiac glycoside cell toxicity

“…Inflammasome activation underlies the pathogenesis of numerous inflammatory diseases; therefore, it was with some surprise that we found currently used drugs that activate this response. Furthermore, toxicity occurred at cardiac glycoside concentrations (digoxin EC 50 , ∼100 n m ) comparable with those that can be observed in human cardiac muscle (>100 ng/g, ∼128 n m (26, 27)). Because macrophages are robustly sensitive to inflammasome activation in general and in response to cardiac glycosides in particular, we reason that this process could impact cardiac tissue–resident macrophages.…”

“…4, A , C , and D ). Although these concentrations far exceed human toxicity thresholds (26, 27) and target additional processes like T cell differentiation and TNF signaling (14, 28, 29), this finding, mirroring the known differential affinities of digoxin for the human versus murine Na,K-ATPase further suggests that the pump could be involved in inflammasome activation.…”

Application of permeability-limited physiologically-based pharmacokinetic models: Part I–digoxin pharmacokinetics incorporating P-glycoprotein-mediated efflux

“…The volume of distribution ( V ss ) was predicted using the method reported by Rodgers and co‐workers 17–19. A number of tissue–plasma partition coefficients ( P t:p ) in human were available in the literature; values of 10.820 and 7.3521,22 were used for adipose and muscle, respectively, whereas the P t:p values for the remaining tissues were predicted according to the Rodgers and Rowland method 18,19…”

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

“…The heart concentration turned out to be one of the highest of the investigated tissues. Karjalainen et al [116] sampled five different parts of the heart: anterior papillary muscle, left ventricular muscle, right ventricular muscle, septal muscle and left auricular muscle. The highest drug concentration was found in the septum.…”

“…Regardless of the site of the heart, the maximum myocardial/blood ratio varied from 17 to 61. It should be mentioned that because of the postmortem drug redistribution, concentrations of blood digoxin were higher than the antemortem values [116]. The question whether the tissue concentration of digoxin differs among adults and infants was raised by Andersson and Wettrell [117].…”