Acetazolamide Blood Concentrations are Excessive in the Elderly: Propensity for Acidosis and Relationship to Renal Function
- 1 April 1989
- journal article
- Published by Wiley in The Journal of Clinical Pharmacology
- Vol. 29 (4), 348-353
- https://doi.org/10.1002/j.1552-4604.1989.tb03340.x
Abstract
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.Keywords
This publication has 14 references indexed in Scilit:
- Toxic interaction between acetazolamide and salicylate: Case reports and a pharmacokinetic explanationClinical Pharmacology & Therapeutics, 1986
- Significant Metabolic Acidosis Induced by AcetazolamideArchives of Internal Medicine, 1985
- Influence of advanced age on the disposition of acetazolamide.British Journal of Clinical Pharmacology, 1985
- Determination of Acetazolamide in Biological Fluids by Reverse-Phase High-Performance Liquid ChromatographyJournal of Pharmaceutical Sciences, 1984
- The Use of Carbonic Anhydrase Inhibitors in Ophthalmology and Clinical MedicinebAnnals of the New York Academy of Sciences, 1984
- Carbonic Anhydrase‐dependent Bicarbonate Transport in the KidneyaAnnals of the New York Academy of Sciences, 1984
- MONITORING ACETAZOLAMIDE TREATMENTActa Ophthalmologica, 1982
- Carbonic Anhydrase Inhibitor Side EffectsAmerican Journal of Ophthalmology, 1977
- Prediction of Creatinine Clearance from Serum CreatinineNephron, 1976
- Oral Administration of a Potent Carbonic Anhydrase Inhibitor (Diamox)New England Journal of Medicine, 1954