Digoxin
Digoxin. Inhibits Na⁺/K⁺-ATPase → intracellular Na⁺ rise → Na⁺/Ca²⁺ exchanger reversal → intracellular Ca²⁺ rise → positive inotropy. Also… Oral half-life 28 h.
Inhibits Na⁺/K⁺-ATPase → intracellular Na⁺ rise → Na⁺/Ca²⁺ exchanger reversal → intracellular Ca²⁺ rise → positive inotropy. Also enhances vagal tone → AV-node slowing (rate control in AF). Narrow therapeutic index: toxic at levels >2 ng/mL. Antidote: digoxin-immune Fab (Digibind).
PK: both flagged values failed, and this is a NARROW-THERAPEUTIC-INDEX drug so the errors matter more than usual. ka 5.84 implies a SEVEN-MINUTE absorption half-life, appears in no abstract, and looks back-fitted to reproduce an observed 1 h time to peak given a 40 h half-life; the measured value is 2.72 /h with a 0.16 h lag, from a stable-label study that also gives the absolute bioavailability of 68.5%. V 490 L was the textbook 7.0 L/kg scaled to 70 kg while its cited source says only "a large volume of distribution" qualitatively; the measured 5.46 L/kg is 382 L, so the stored figure OVERSTATED A LOADING DOSE BY ABOUT 28%. The 40 h half-life is stated nowhere either — the review says "between 26 and 45 hours" and 40 is not the midpoint. F 0.7 was a range lower endpoint AND the wrong quantity, describing absorption rather than systemic availability. HALF-LIFE AND VOLUME MUST TRAVEL TOGETHER: 27.9 h pairs with 5.46 L/kg, while the 42 h in the literature pairs with a roughly 13 L/kg terminal volume; grafting one onto the other would misstate clearance by about half. The effect-compartment value verifies and is human, but its endpoint is RATE CONTROL in atrial fibrillation rather than inotropy, and effect tracks the deep peripheral compartment rather than plasma.
Pharmacokinetics
- Oral — t½ 27.9 h · F 69% · ka 2.72 h⁻¹ · Vd 382 L
- IV — t½ 27.9 h · F 100% · Vd 382 L
Sources: PMID:322907, PMID:6832200, PMID:358815, PMID:458556, PMID:5771186