ArticleBritish journal of clinical pharmacology2019
Impact of reduced P-glycoprotein function on digoxin concentrations in patients with dementia.
Article in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed, 3 citations in OpenAlex.
- Review
- Potential Links Between Aging, Mitochondrial Dysfunction, and Drug Transporter Function-Molecular Mechanisms and Pharmacokinetic Implications.International journal of molecular sciences · 2026Review
- Cognitive impairment and risk of dementia in heart failure: the exuberating role of digoxin.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Computational prognostic evaluation of Alzheimer's drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches.Scientific reports · 2023Article
- Impact of reduced P-glycoprotein function on digoxin concentrations in patients with dementia.British journal of clinical pharmacology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsPatients with Alzheimer's disease (AD), the most common form of dementia, have reduced P-glycoprotein (P-gp) function at the blood-brain barrier. However, the effect of AD on P-gp function in peripheral organs, and the impact on medication efficacy and toxicity is unknown. In this study, clinical chart review and physiologically based pharmacokinetic (PBPK) modelling were employed to determine whether disease-associated changes in P-gp could be assessed from clinically measured digoxin concentrations in patients without and with dementia.
methodsA retrospective chart review was conducted to compare digoxin dose and concentrations between cohorts. A PBPK model was developed to simulate changes in digoxin concentrations at single and multiple 62.5 and 125 μg/d doses due to reduced P-gp function in peripheral organs.
resultsDigoxin concentrations were similar between the nondementia (n = 75) and dementia (n = 72) cohorts (mean ± standard deviation; 0.64 ± 0.31 and 0.60 ± 0.34 ng/mL, respectively; -0.06 to 0.15, 95% confidence interval of difference). PBPK simulations showed that reduced P-gp function resulted in a significant increase in digoxin exposure (AUC), but not in C
conclusionClinically measured digoxin concentrations were not statistically different in patients with dementia. Based on PBPK simulations, digoxin AUC may need to be evaluated to adequately assess the impact of reduced P-gp function in peripheral organs.
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