Urinary excretion of acetazolamide in healthy volunteers after short- and long-term exposure to high altitude.

Acetazolamide is recommended for the prophylaxis of acute mountain sickness symptoms which sets in on climbing to high altitudes (H) above 2,500 m. It is primarily excreted unchanged in urine. In a previous study, we reported on the changes in urinary excretion of meperidine and its metabolite normeperidine on exposure to high altitude. In this study, we investigated the effect on urinary excretion of acetazolamide. The study was carried out in three groups of 12 healthy male volunteers each: at sea level (group L), these same volunteers the day after arrival at high altitude of 4,360 m (group HA), and subjects residing for approximately 10 months at high altitude (group HC). Urine was collected for the periods of 0-2, 2-4, 4-8, 8-12, 12-24 and 24-36 h after peroral administration of a single 250 mg dose. Urinary pH was measured and the concentrations of acetazolamide were determined. There were no significant changes observed in the amount of acetazolamide excreted in urine over 36 h. The urinary pH ranged from 4.5 to 7.8 for L, from 4.2 to 6.9 for HA and from 3.1 to 6.7 for HC. The Fel (fraction eliminated unchanged in urine) was calculated from the amount excreted in 36 h in urine and dose, assuming a bioavailability of 1 based on literature data. No significant changes in Fel were seen.