Li Xiang-Yang, Liu Yong-Nian, Wang Xue-Jun, Zhu Jun-Bo, Yuan Ming, Li Yong-Ping, Li Yong-Fang
Department of Pharmacy, Qinghai University Medical College, Xining, China.
Eur J Drug Metab Pharmacokinet. 2012 Dec;37(4):263-9. doi: 10.1007/s13318-012-0090-0. Epub 2012 Mar 30.
The aim of this study was to investigate the pharmacokinetics of sulfamethoxazole in native Han and Tibetan healthy Chinese subjects living chronically at high altitude. An open-labeled, controlled, prospective study was conducted in healthy Chinese male volunteers. Sulfamethoxazole 1,200 mg was administered orally to two groups: native Han and Tibetan volunteers living at high altitude (2,500-3,900 m [8,200-12,800 ft]). 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 h after study drug administration. Sulfamethoxazole in whole blood, plasma, and plasma water, and metabolite N (4)-acetyl-sulfamethoxazole in plasma were determined by HPLC. Tolerability was determined using blood chemistry testing, continuous 12-lead electrocardiogram, and blood pressure monitoring. The protein binding was significantly higher in the native Tibetan group (70.5 %) compared to the native Han group (67.3 %) (p < 0.05). The binding of sulfamethoxazole to red blood cells was 7.4 and 8.3 % in the native Han and native Tibetan groups, respectively. There was no significant difference between the two groups. The AUC(0-∞) was significantly lower in the native Tibetan group compared to the native Han group (p < 0.05), and other pharmacokinetics parameters were found to have no significant difference between the two groups. This study found little changes in the disposition of sulfamethoxazole in these native healthy Tibetan Chinese subjects living at high altitude in comparison to native healthy Han Chinese subjects living at high altitude.
本研究旨在调查磺胺甲恶唑在长期居住于高海拔地区的中国汉族和藏族健康受试者中的药代动力学。对中国健康男性志愿者进行了一项开放标签、对照、前瞻性研究。向两组受试者口服1200mg磺胺甲恶唑：居住在高海拔地区（2500 - 3900米[8200 - 12800英尺]）的汉族和藏族志愿者。在研究药物给药前（基线）以及给药后0.25、0.5、0.75、1、1.5、2、3、4、6、8、12、24、36和48小时，从留置静脉导管采集血样至肝素化管中。通过高效液相色谱法测定全血、血浆和血浆水中的磺胺甲恶唑以及血浆中的代谢物N（4）-乙酰磺胺甲恶唑。通过血液化学检测、连续12导联心电图和血压监测来确定耐受性。藏族组的蛋白结合率（70.5%）显著高于汉族组（67.3%）（p < 0.05）。汉族和藏族组中磺胺甲恶唑与红细胞的结合率分别为7.4%和8.3%。两组之间无显著差异。藏族组的AUC(0 - ∞)显著低于汉族组（p < 0.05），且发现两组之间的其他药代动力学参数无显著差异。本研究发现，与居住在高海拔地区的汉族健康受试者相比，居住在高海拔地区的藏族健康受试者中磺胺甲恶唑的处置变化不大。
