Pharmacokinetics of sulfamethoxazole in healthy Han volunteers living at plain and in native Han and Tibetan healthy volunteers living at high altitude

The paper is to report the pharmacokinetics of sulfamethoxazole in healthy Han volunteers living at plain (PH) and native Han and Tibetan healthy volunteers living at high altitude (HNH and HNT).  After healthy volunteers were administrated orally cotrimoxazole tablets, plasma concentration of sulfamethoxazole and metabolite N⁴-acetylsulfamethoxazole was determined by RP-HPLC, and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters.  The main pharmacokinetic parameters t_1/2 of sulfamethoxazole in PH, HNH and HNT were, respectively, 9.30 ± 1.11, 10.99 ± 1.23 and  10.44 ± 1.05 h; t_max were 1.4 ± 0.3, 2.0 ± 1.1 and 1.8 ± 0.4 h; C_max were 94.42 ± 15.26, 89.33 ± 7.67 and 87.43 ± 11.61 μg·mL⁻¹; AUC_0−t were 1 202.5 ± 238.3, 1 434.7 ± 193.9 and 1 302.8 ± 103.0 μg·h·mL⁻¹; AUC_0−∞ were 1 240.7 ± 255.3, 1 511.5 ± 211.9 and 1 363.9 ± 116.5 μg·h·mL⁻¹; CL were 1.01 ± 0.22, 0.81 ± 0.12 and  0.89 ± 0.08 L·h⁻¹·kg⁻¹; V were 13.27 ± 1.73, 12.81 ± 2.15 and 13.28 ± 1.20 L·kg⁻¹.  Sulfamethoxazole pharmacokinetic parameters of HNH and HNT were significantly different from that of PH.  The t_1/2 was significantly higher and the CL was significantly lower in HNH and HNT than that in PH, and the AUC_0−∞ was significantly lower in HNT compared with HNH.  This study found significant changes in the disposition of sulfamethoxazole under the special environment of high altitude hypoxia.  This finding may provide some references for clinical rational application of sulfamethoxazole in HNH and HNT.