Key result
A review of cardiac surgery and postmortem studies provides insight into the cardiac distribution of over 200 drugs, highlighting multiple mechanisms involved in drug distribution within the heart.
This review highlights the complexity of drug distribution into human cardiac tissue, emphasizing that plasma concentrations may not accurately reflect myocardial tissue levels for over 200 drugs.
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Cardiac Kp data may refine distribution estimates beyond plasma; leaves open prospective validation against clinical or electrophysiological outcomes.
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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Tylutki et al. (2015) conducted a review in Drug distribution in human cardiac tissue. Various drugs (antibiotics, antifungals, anticancer, antiarrhythmics) vs. Plasma concentration was evaluated on Tissue to plasma partition coefficients (Kp) and drug concentrations in human cardiac tissue. A review of cardiac surgery and postmortem studies provides insight into the cardiac distribution of over 200 drugs, highlighting multiple mechanisms involved in drug distribution within the heart.
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