Abstract
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 AUC0–∞ 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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arancibia A, Paulos C, Chávez J, Ritschel WA (2003) Pharmacokinetics of lithium in healthy volunteers after exposure to high altitude. Int J Clin Pharmacol Ther 41:200–206
Aslam M, Khan MZ (1996) The role of drugs in high altitude disorders. J Pak Med Assoc 46:90–92
Beall CM, Goldstein MC (1987) Hemoglobin concentration of pastoral nomads permanently resident at 4,850–5,450 meters in Tibet. Am J Phys Anthropol 73:433–438
Beall CM, Brittenham GM, Strohl KP, Blangero J, Williams-Blangero S, Goldstein MC, Decker MJ, Vargas E, Villena M, Soria R, Alarcon AM, Gonzales C (1998) Hemoglobin concentration of high-altitude Tibetans and Bolivian Aymara. Am J Phys Anthropol 106:385–400
Benet LZ, Kroetz DL, Sheiner LB (1990) Pharmacokinetics: the dynamics of drug absorption, distribution, and elimination. In: Gilman AG, Rall TW, Nies AS, Taylor P (eds) Goodman and Gilman’s the pharmacological basis of therapeutics, 8th edn. Pergamon Press, New York
Center for Drug Evaluation, State Food and Drug Administration of China (2005) Technical guidelines of chemical drugs in clinical pharmacokinetics studies. http://www.sda.gov.cn/gsz05106/07.pdf
Chen ZY, Zheng QS, Sun RY (2002) Functions of the DAS software for pharmacological calculation. Chin J Clin Pharmacol Ther 7:562–564
Chinese Medical Association for High Altitude Medicine (1996) Recommendation for the classification and diagnostic criteria of high altitude disease in China. Chin High Alt Med J 6:2–5
Cribb AE, Nakamura H, Grant DM, Miller MA, Spielberg SP (1993) Role of polymorphic and monomorphic human arylamine N-acetyltransferases in determining sulfamethoxazole metabolism. Biochem Pharmacol 45:1277–1282
Duplain H, Sartori C, Scherrer U (2007) High-altitude related illness. Rev Med Suisse 3:1766–1769
Gallagher SA, Hackett PH (2004) High altitude illness. Emerg Med Clin North Am 22:329–355
Ha Z, Zhu Y, Zhang X, Cui J, Zhang S, Ma Y, Wang W, Jian X (2002) The effect of rhodiola and acetazolamide on the sleep architecture and blood oxygen saturation in men living at high altitude. Zhonghua Jie He He Hu Xi Za Zhi 25:527–530
Jung TR, Hwang SW, Lee JU, Cho MJ, Kim Y, Yoo TW (2001) Comparative consistency between obesity determination standards using body mass index and ideal body weight. J Korean Acad Fam Med 22:1765–1771
Kamimori GH, Eddington ND, Hoyt RW, Fulco CS, Lugo S, Durkot MJ, Brunhart AE, Cymerman A (1995) Effects of altitude (4300 m) on the pharmacokinetics of caffeine and cardio-green in humans. Eur J Clin Pharmacol 48:167–170
Li XY, Gao F, Li ZQ, Guan W, Feng WL, Ge RL (2009) 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-labeled, controlled, prospective study. Clin Ther 31:2744–2754
Luks AM, Swenson ER (2008) Medication and dosage considerations in the prophylaxis and treatment of high-altitude illness. Chest 133:744–755
Masters PA, O’Bryan TA, Zurlo J, Miller DQ, Joshi N (2003) Trimethoprim–sulfamethoxazole revisited. Arch Intern Med 163:402–410
Monge C, Leon-Velarde F (1991) Physiological adaptation to high altitude: oxygen transport in mammals and birds. Physiol Rev 71:1135–1172
Reilly TP, Woster PM, Svensson CK (1999) Methemoglobin formation by hydroxylamine metabolites of sulfamethoxazole and dapsone: Implications for differences in adverse drug reactions. J Pharmacol Exp Ther 288:951–959
Ritschel WA (1992) Binding of drugs to biological material. In: Ritschel WA (ed) Handbook of Basic pharmacokinetics—including clinical applications, 4th edn. Drug Intelligence Publications, Hamilton, II, pp 153
Ritschel WA, Paulos C, Arancibia A, Pezzani M, Agrawal MA, Wetzelsberger KM, Lücker PW (1996a) Pharmacokinetics of meperidine in healthy volunteers after short- and long-term exposure to high altitude. J Clin Pharmacol 36:610–616
Ritschel WA, Paulos C, Arancibia A, Pezzani M, Agrawal MA, Wetzelsberger KM, Lücker PW (1996b) Urinary excretion of meperidine and normeperidine in man upon acute and chronic exposure to high altitude. Methods Find Exp Clin Pharmacol 18:49–53
Ritschel WA, Paulos C, Arancibia A, Agrawal MA, Wetzelsberger KM, Lucker PW (1998a) Pharmacokinetics of acetazolamide in healthy volunteers after short-and long-term exposure to high altitude. J Clin Pharmacol 38:533–539
Ritschel WA, Paulos C, Arancibia, Agrawal MA, Wetzelsberger KM and Lucker PW (1998b) Urinary excretion of acetazolamide in healthy volunteers after short-and long-term exposure to high altitude. Methods Find Exp Clin Pharmacol 20:133–137
Wu TY (2005) Chronic mountain sickness on the Qinghai-Tibetan plateau. Chin Med J 118:161–168
Yu CH (2007) SPSS and Statistic Analysis. Publishing House of Electronics Industry, Beijing
Zhang YB, Wang Y, Liu XL (1984) Mountain Sickness. Publishing House of Qinghai People, Qinghai
Zubieta-Castillo G Sr, Zubieta-Calleja GR Jr, Zubieta-Calleja L (2006) Chronic mountain sickness: the reaction of physical disorders to chronic hypoxia. J Physiol Pharmacol 57(Suppl 4):431–442
Acknowledgments
The authors express their sincere thanks to the Red Cross Hospital of Qinghai for their support, transportation, and housing at the investigation site to facilitate this study. This study was supported by the National Natural Science Fund of China (No. 30960457) and Program for New Century Excellent Talents in University of the Ministry of Education of China (No. NCET-10-0917). The sponsor did not play any major role in the design, conduct, or analysis of the study. The authors did not receive any funding for conducting the study. The authors have indicated that they have no other conflicts of interest regarding the content of this article.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Li, XY., Liu, YN., Wang, XJ. et al. Comparison of the pharmacokinetics of sulfamethoxazole in native Han and Tibetan male Chinese volunteers living at high altitude. Eur J Drug Metab Pharmacokinet 37, 263–269 (2012). https://doi.org/10.1007/s13318-012-0090-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13318-012-0090-0