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Pharmacokinetics in the Fontan Circulation: a multi-organ puzzle
Panayotis K Vlachakis1,2, Maria Drakopoulou1,2, Panagiotis Theofilis1,2
1First Department of Cardiology, Hippokration General Hospital of Athens, National and Kapodistrian University of Athens, Athens, Greece.
European Heart Journal. Cardiovascular Pharmacotherapy
|August 10, 2026
Summary
Patients with Fontan circulation have altered drug processing due to their unique physiology. Current prescribing practices often fail to account for these pharmacokinetic changes, impacting medication effectiveness and safety.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Drug Metabolism
Background:
- Fontan circulation presents unique physiological challenges affecting drug disposition.
- Altered hemodynamics, liver function, and protein binding impact pharmacokinetics.
- Current prescribing practices often overlook these Fontan-specific alterations.
Purpose of the Study:
- To review the pharmacokinetic alterations in patients with Fontan circulation.
- To evaluate the impact of these changes on major cardiovascular drug classes.
- To propose a research agenda for Fontan-specific pharmacokinetics.
Main Methods:
- Literature review of pharmacokinetic alterations in Fontan patients.
- Examination of mechanistic basis for altered drug disposition.
- Evaluation of existing drug-class evidence.
Main Results:
- Fontan-associated liver disease reduces first-pass metabolism, increasing drug bioavailability.
- Hypoalbuminemia increases the free fraction of protein-bound drugs.
- Reduced cardiac output and renal perfusion affect drug distribution and clearance.
Conclusions:
- Pharmacokinetic changes in Fontan patients necessitate tailored prescribing strategies.
- Further research, including physiologically-based modeling and dedicated trials, is crucial.
- Optimizing drug therapy requires accounting for Fontan-specific pharmacokinetic alterations.
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