Nadolol
Nadolol. Long-acting non-selective β-adrenergic blocker. Renally cleared (no CYP), preferred in liver disease. Used for hypertension, angina… Oral half-life 14 h.
Long-acting non-selective β-adrenergic blocker. Renally cleared (no CYP), preferred in liver disease. Used for hypertension, angina, esophageal varices prophylaxis. Once-daily dosing. PK (Corgard label + Kalsoom 2022 systematic review PMID:35243668): F ~30–35% (poor oral absorption — hydrophilic β-blocker), apparent Vd ~1.9 L/kg (~135 L), t½ 17–23 h (allowing once-daily dosing), Tmax 3–4 h. ~75% renally excreted unchanged — accumulates in renal impairment. Steady state by day 3. Binds primarily to α₁-acid glycoprotein, free fraction ~0.7.
PK: ITS CITATION WAS AN INTRAVENOUS-ONLY STUDY AND THREE OF THE FOUR STORED VALUES WERE ORAL. That paper entire numeric content is "total body clearance (219 to 250 ml.min-1) ... half-life (8.8 to 9.4 h), and steady-state volume of distribution (Vss) (147 to 157 l)" — no bioavailability, no absorption rate, no single-valued volume. t-half 9.1 was the EXACT ARITHMETIC MIDPOINT of that range; V 135 L appears in no abstract at all, matching neither the Vss range nor its midpoint nor any per-kg conversion. F moves to the verbatim "oral doses of nadolol-14C were absorbed to the extent of 33.6+/-2.4 per cent". THE HALF-LIFE MOVES BECAUSE THIS DRUG IS FLIP-FLOP: its oral terminal half-life exceeds its intravenous one in every paired dataset including the same subjects, "Terminal plasma half-times after oral and intravenous doses were an average of 12.2 and 9.8 hours, respectively". V 284 L IS AN APPARENT, FLIP-FLOP VOLUME and contradicts the published intravenous 2.09 L/kg; that is the price of one compartment, and it is stated rather than hidden. Checked against an independent study, the new set predicts 59.6 and 119.2 ng/mL at 60 and 120 mg against an observed "69 +/- 15 to 132 +/- 27", where the old set was 31% and 37% high. A HARDER LIMIT IS RECORDED SEPARATELY: nadolol is not superposable.
Pharmacokinetics
- Oral — t½ 14 h · F 34% · ka 0.85 h⁻¹ · Vd 284 L
Sources: PMID:15655528, PMID:3366166, PMID:6146679, PMID:16040, PMID:6714285, PMID:2235896