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Population Pharmacokinetic Studies of Digoxin in Adult Patients: A Systematic Review

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Abstract

Background

Digoxin is a cardiac glycoside that was introduced to cardiovascular medicine more than 200 years ago. Its use is associated with large variability, which complicates achieving the desired therapeutic outcomes.

Objectives

To present a synthesis of the available literature on the population pharmacokinetics of digoxin in adults and to identify the sources of variability in its pharmacokinetics.

Methods

This is a PROSPERO registered systematic review (CRD42018105300). A literature search was conducted using the ISI Web of Science, Science Direct, PubMed, and SCOPUS databases to identify digoxin population pharmacokinetic studies of adults that utilized the nonlinear mixed-effect modeling approach.

Results

Sixteen articles were included in the present analysis. Only two studies were conducted in elderly subjects as a separate population. Both the pharmacokinetics and pharmacodynamics of digoxin were investigated in one study. Furthermore, the reviewed studies were mostly conducted in East Asian populations (68.8%). Digoxin's pharmacokinetics were usually described by a one-compartment model because of the nature of the collected data. Weight, age, kidney function, presence of heart failure, and co-administered medications such as calcium channel blockers were the most commonly identified predictors of digoxin clearance. The value of apparent clearance in a typical study individual ranged from 0.005 to 0.2 l/h/kg, while the value of the apparent volume of distribution ranged from 3.14 to 15.2 l/kg. The quality of model evaluation was deemed excellent only in 31.3% of the studies.

Conclusion

This review provides information about variables that need to be considered when prescribing digoxin. The results highlight the need for prospective studies that allow two-compartment pharmacokinetic/pharmacodynamic models to be established, with a special focus on the elderly subpopulation.

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Author information

Authors and Affiliations

  1. Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, University of Jordan, Amman, 11942, Jordan

    Mariam Abdel Jalil & Khawla Abu-Hammour

  2. Department of Pharmacology, Faculty of Medicine, University of Jordan, Amman, Jordan

    Noura Abdullah

  3. Department of Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan

    Mervat Alsous

Authors
  1. Mariam Abdel Jalil
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  2. Noura Abdullah
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  3. Mervat Alsous
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  4. Khawla Abu-Hammour
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Corresponding author

Correspondence to Mariam Abdel Jalil.

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Funding

No funding was received to conduct this review.

Conflicts of interest

The authors have no conflicts to declare

Availability of data and material

Extracted data are presented in the text.

Code availability

Not applicable.

Authors' contributions

Conceptualization: M.A.J. Conducting the review: M.A.J., N.A., M.A., K.A. Data analysis: M.A.J., N.A., M.A. Writing the manuscript: M.A.J., N.A., M.A., K.A. Reviewing and approving the manuscript: M.A.J., N.A., M.A., K.A.

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Abdel Jalil, M., Abdullah, N., Alsous, M. et al. Population Pharmacokinetic Studies of Digoxin in Adult Patients: A Systematic Review. Eur J Drug Metab Pharmacokinet 46, 325–342 (2021). https://doi.org/10.1007/s13318-021-00672-6

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  • DOI: https://doi.org/10.1007/s13318-021-00672-6

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