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Influence of advanced age on the disposition of acetazolamide.

The disposition kinetics of acetazolamide (AZ) has been studied in four young and four elderly healthy volunteers, each of whom received an intravenous bolus dose of 5 mg/kg. The concentration time profile of AZ was determined in plasma, plasma ultrafiltrate, erythrocytes and urine. While the mean area under unbound plasma concentration-time curves was 81% higher in elderly subjects, areas based on total drug concentrations were similar in both groups. The mean renal plasma clearance was similar in both groups. The mean renal plasma clearance was similar between young and old for total AZ, but was significantly lower in the elderly for unbound drug (8.88 ml min-1 kg-1 vs 15.7 ml min-1 kg-1). Renal clearance of unbound AZ correlated well with creatinine clearance (r = 0.846, P less than 0.01). Peak erythrocyte levels were 45% higher in the elderly group (37.2 micrograms/ml vs 25.3 micrograms/ml) and were paralleled by a 46% increase in the mean area under the erythrocyte concentration-time curve for this age group. The unbound fraction of AZ in plasma was significantly greater in elderly than younger subjects (6.9 vs 4.1%, P less than 0.05). Integrated AZ erythrocyte concentrations correlated positively with AZ free fraction in plasma and inversely with its unbound renal clearance. These observed differences in AZ disposition between elderly and young have served to clarify host factors which may importantly influence susceptibility to adverse effects.