URINARY-EXCRETION OF ACETAZOLAMIDE IN HEALTHY-VOLUNTEERS AFTER SHORT-TERM AND LONG-TERM EXPOSURE TO HIGH-ALTITUDE

Acetazolamide is recommended for the prophylaxis of acute mountain sic kness symptoms which sets in on climbing to high altitudes (H) above 2 ,500 m. It is primarily excreted unchanged in urine. In a previous stu dy, we reported on the changes in urinary excretion of meperidine and its metabolite normeperidine on exposure to high altitude. In this stu dy, we investigated the effect on urinary excretion of acetazolamide. The study was carried out in three groups of 12 healthy male volunteer s each: at sea level (group L), these same volunteers the day after ar rival at high altitude of 4,360 m (group HA), and subjects residing fo r similar to 10 months at high altitude (group HC). Urine was collecte d for the periods of 0-2, 2-4, 4-8 8-12, 12-24 and 24-36 h after peror al administration of a single 250 mg dose. Urinary pH was measured and the concentrations of acetazolamide were determined. There were no si gnificant changes observed in the amount of acetazolamide excreted in urine over 36 h. The pH 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 F-el (fraction elimi nated unchanged in urine) was calculated from the amount excreted in 3 6 h in urine and dose, assuming a bioavailability of 1 based on litera ture data. No significant changes in F-el were seen. (C) 1998 Prous Sc ience. All rights reserved.