P-glycoprotein (P-gp) is an ATP-dependent efflux membrane transporter involved in many drug pharmacokinetics in humans. Decreasing its expression could enhance the bioavailability of substrates as digoxin. We have recently found that human recombinant interleukin-2 (rIL2) in vivo decreases P-gp expression in intestine and brain of mice and modifies oral digoxin pharmacokinetics. The aim of the ...

OBJECTIVES The aim of this study was to assess temporal trends and factors associated with digoxin use at discharge among patients admitted with heart failure (HF). BACKGROUND Digoxin has class IIa recommendations for treating HF with reduced ejection fraction (HFrEF) in the United States. Digoxin use, temporal trends, and clinical characteristics of HF patients in current clinical practice i...

To clarify the suppressant action of diphenylhydantoin (DPH) on digitalis-induced arrhythmias we studied effects of DPH and digoxin, alone and in combination, on contractile force, sodium-potassium adenosinetriphosphatase (Na + -K ATPase) activity, and potassium (K) balance in dog hearts perfused with Krebs-Ringer's solution. Neither control perfusion nor DPH alone (3 X 10"M) altered Na + -K AT...

Heart failure (HF) is the leading cause of death in the world and digoxin remains one of the oldest therapies for HF. However, its safety and efficacy have been controversial since its initial use and there is uncertainty about its long-term efficacy and safety. Recently, the repositioning of cardiac glycosides is to function in anti-tumor activity via multiple working pathways. It is interesti...

There is wide variation in how patients respond to therapeutics. Factors that contribute to pharmacokinetic variations include disease, genetics, drugs, age, and diet. The purpose of this study was to determine the effect of calorie restriction on the expression of Abcb1a in the intestine and whether calorie restriction can alter the absorption of an Abcb1a substrate (i.e., digoxin) in mice. Te...

BACKGROUND This study was carried out as part of a European Union funded project (PharmDIS-e+), to develop and evaluate software aimed at assisting physicians with drug dosing. A drug that causes particular problems with drug dosing in primary care is digoxin because of its narrow therapeutic range and low therapeutic index. OBJECTIVES To determine (i) accuracy of the PharmDIS-e+ software for...

BACKGROUND The therapeutic range for digoxin in heart failure has recently changed to become lower and narrower, and the new range is associated with improved mortality. However, dosing methods have not been modified to reflect this change. In this study, we sought to develop a new method to determine the initial dose of digoxin in patients with heart failure. METHODS Over a 6-month period, m...

OBJECTIVES This study aims to assess whether digoxin has a different effect on mortality risk for women than it does for men in patients with heart failure (HF). DESIGN This study uses the UK-based The Health Information Network population database in a cohort study of the impact of digoxin exposure on mortality for men and women who carry the diagnosis of HF. Digoxin exposure was assessed ba...

Because rifampin (RIF) induces hepatic enzymes and inhibits uptake transporters, dosing a drug that is a dual substrate of enzymes and uptake transporters on the final day of an inducing regimen should exhibit less inductive effect than dosing on the following day in the absence of RIF, since RIF decreases drug uptake into liver. In vitro and in vivo rat studies were conducted using digoxin as ...

BACKGROUND Digoxin was found to inhibit prostate cancer (PCa) growth via the inhibition of HIF-1α synthesis in a mouse model. We hypothesized that a therapeutic dose of digoxin could inhibit human PCa growth and disease progression. METHODS An open label, single arm pilot study was performed. Patients (pts) with non-metastatic, biochemically relapsed PCa with prostate specific antigen doublin...