Comparison of the pharmacokinetics of sulfamethoxazole in male chinese volunteers at low altitude and acute exposure to high altitude versus subjects living chronically at high altitude: An open-label, controlled, prospective study

Abstract Background: Sulfamethoxazole is an antibacterial sulfonamide used primarily for the treatment of a wide variety of bacterial infections in combination with trimethoprim. Despite being used as prophylactic treatment for respiratory infections associated with high altitude, little information...

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Veröffentlicht in:Clinical therapeutics 2009-11, Vol.31 (11), p.2744-2754
Hauptverfasser: Li, Xiang-Yang, PhD, Gao, Fen, MS, Li, Zhan-Quan, MS, Guan, Wei, MS, Feng, Wei-Li, BS, Ge, Ri-Li, MD
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Sprache:eng
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Zusammenfassung:Abstract Background: Sulfamethoxazole is an antibacterial sulfonamide used primarily for the treatment of a wide variety of bacterial infections in combination with trimethoprim. Despite being used as prophylactic treatment for respiratory infections associated with high altitude, little information is available on the pharmacokinetic properties of sulfamethoxazole in subjects living at high altitude, especially in a Chinese population. Objective: This study was conducted to investigate the pharmacokinetics of sulfamethoxazole in healthy Chinese subjects after acute and chronic exposure to high altitude. Methods: An open-label, controlled, prospective study was conducted in healthy Chinese male volunteers. Sulfamethoxazole 1200 mg was administered orally to volunteers in 3 groups: those residing at low altitude (~400 m [~1300 ft]); these same volunteers after 16 hours (acute) of exposure to high altitude (~3780 m [~12,400 ft]); and a separate group of volunteers who had been living at high altitude (~3780 m) for ≥1 year (chronic). The phases of the low-altitude and acute-exposure groups were separated by a 1-week washout period. Blood samples were collected from an indwelling venous catheter into heparinized tubes before (baseline) study drug administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours after study drug administration. Sulfamethoxazole in whole blood, plasma, and plasma water, and its metabolite, N4 -acetyl-sulfamethoxazole, in plasma were determined by HPLC. Tolerability was determined using blood chemistry testing, continuous 12-lead ECG, and blood pressure monitoring. Results: A total of 23 healthy Chinese male volunteers living at low altitude (race, all Han Chinese; mean [SD] age, 20.4 [1.1] years [range, 19–24 years]; weight, 64.2 [5.9] kg [range, 56.0–75.0 kg]; and height, 172.1 [4.9] cm [range, 163.0–180.0 cm]) and 21 healthy Chinese male volunteers living at high altitude (race, all Han Chinese; mean [SD] age, 21.2 [1.3] years [range, 19–24 years]; weight, 62.4 [8.2] kg [range, 50.0–75.0 kg]; and height, 171.4 [5.8] cm [range, 162.0–182.0 cm]) were enrolled in the study; 20 from each group completed the study. Concentration of sulfamethoxazole in plasma water decreased significantly after exposure to high altitude; therefore, the protein binding was significantly higher in the acute- (80.4%) and chronic-exposure (72.5%) groups compared with the low-altitude group (65.7%; both, P < 0.001). The binding of su
ISSN:0149-2918
1879-114X
DOI:10.1016/j.clinthera.2009.11.019