Abstract / Summary
Abstract Purpose Free digoxin falls after digoxin-specific antibody fragments (Fab), then rebounds. A fixed additional clearance carries no antibody or complex mass, so it cannot give the duration of suppression. We asked when the rebound peaks, how high it rises, and how renal function changes both. Methods Digoxin occupied central, fast-tissue and deep-tissue compartments and Fab one, with an explicit Fab–digoxin complex at mass-action equilibrium. Exchange and elimination tracked non-Fab-bound plasma digoxin and creatinine clearance. Four renal strata and an acute-kidney-injury scenario were simulated at the labelled dose against a fixed-clearance comparator. Results In the reference scenario (labelled dose, single ingestion), free digoxin peaked 90.0 h after Fab with normal renal function and 291.5 h with dialysis-dependent kidney failure (ratio 3.24), and 187.0 h when renal function fell acutely; the fixed-clearance comparator gave 66.0 h at all strata (ratio 1.00). In the dose-aligned scenario matched to the published cohort, the rebound peak was 0.361 nmol/L at 1×10¹⁰ M⁻¹, 4.70-fold below the observed mean of 1.7 ± 1.3 nmol/L, and 1.083 nmol/L at 1×10⁹ M⁻¹. Free digoxin stayed below 2.6 nmol/L in all strata except at sub-neutralising doses. Terminal half-life (1.83, 3.55 d) and convergence (6.9×10⁻⁷) met criteria. Conclusion Renal function, not dose alone, set when free digoxin rebounded; a fixed-clearance construct is flat by construction. Rebound amplitude depended strongly on antibody affinity; the labelled upper bound was incompatible with observed peaks. These predictions did not meet pre-specified criteria; no dosing recommendation follows.