Acetazolamide
Acetazolamide. Carbonic anhydrase inhibitor — blocks proximal tubule HCO3- reabsorption + reduces aqueous humor production + reduces CSF… Oral half-life 6 h.
Carbonic anhydrase inhibitor — blocks proximal tubule HCO3- reabsorption + reduces aqueous humor production + reduces CSF production. Used for glaucoma, altitude sickness prophylaxis, idiopathic intracranial hypertension. Metabolic acidosis + paresthesias common.
PK: both cited papers are unusable — one is a narrative review of off-label uses, the other an IN-VITRO medicinal-chemistry paper using this drug only as a reference inhibitor — so all five values were unsupported and the stored 8 h was the upper endpoint of that review 4-8 h range. NO SINGLE HALF-LIFE IS DEFENSIBLE: the therapeutic-dose value is 3 to 6 h but a microdose gives 24.5 h, an EIGHT-FOLD DOSE DEPENDENCE, because the erythrocyte carbonic-anhydrase binding capacity saturates. The upper therapeutic endpoint is stored. V 17 L IS A MATRIX ARTEFACT and is deleted: the dominant compartment is the ERYTHROCYTE, whose own sequestration half-life is 50.2 h and whose concentrations run five to ten times plasma, and the apparent volume demonstrably halves when salicylate displaces the drug. For a related carbonic-anhydrase inhibitor, fitting the same data in plasma against whole blood gave volumes of 559 and 7.6 L. F is dropped: the only bioavailability studies found are relative lot-comparisons, one of which reports bio-INEQUIVALENCE between tablet lots, and absorption rate is likewise formulation-lot-specific.
Pharmacokinetics
- Oral — t½ 6 h
- IV — t½ 6 h · F 100%
Sources: PMID:29626002, PMID:30878812, PMID:27300254, PMID:3986087, PMID:23683608