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Acetazolamide Blood Concentrations are Excessive in the Elderly: Propensity for Acidosis and Relationship to Renal Function

Elderly glaucoma patients are often treated with acetazolamide, a carbonic anhydrase inhibitor with clearance dependent on renal function. A high incidence of metabolic acidosis and other adverse effects have been noted among these patients but the reasons for this have not been explained. We hypothesized that commonly used doses of acetazolamide among the elderly result in excessive blood concentrations and that these concentrations are related to acid‐base disturbances. We measured steady‐state acetazolamide levels in plasma, plasma ultrafiltrate (unbound), and erythrocytes among 12 elderly subjects (79.2 ± 7.6 years old). Mean plasma (18.9 ± 10.9 ug/mL) and ultrafiltrate concentrations (1.0 ± 0.7 ug/mL) exceeded the therapeutic range (plasma 5–10 ug/mL; ultrafiltrate 0.25–0.50 ug/mL) for glaucoma control by two fold and were elevated in 75% of subjects. Plasma and ultrafiltrate acetazolamide levels significantly correlated with the dose adjusted for creatinine clearance (r = 0.91, P < 0.001; r = 0.89, P < 0.001, respectively). Acidotic subjects (serum total carbon dioxide ≤ 22 mEq/L) tended to have higher plasma, ultrafiltrate, and erythrocyte acetazolamide levels compared with nonacidotic subjects. Serum total carbon dioxide levels were significantly correlated with erythrocyte acetazolamide concentrations (r = −0.75, P = 0.03). The ratio of erythrocyte acetazolamide concentration to creatinine clearance separated acidotic from nonacidotic subjects (P < 0.01). These findings suggest that some of the adverse effects of acetazolamide can be avoided by reducing the dose to compensate for age‐related reductions in renal drug clearance.