title: [Pharmacokinetics of sulfamethoxazole in healthy Han volunteers living at plain and in native Han and Tibetan healthy volunteers living at high altitude].
abstract: 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; tmax were 1.4 +/- 0.3, 2.0 +/- 1.1 and 1.8 +/- 0.4 h; Cmax were 94.42 +/- 15.26, 89.33 +/- 7.67 and 87.43 +/- 11.61 micro x mL(-1); AUC(0-t) were 1202.5 +/- 238.3, 1 434.7 +/- 193.9 and 1302.8 +/- 103.0 microg x h x mL(-1); AUC(0-infinity) were 1240.7 +/- 255.3, 1511.5 +/- 211.9 and 1363.9 +/- 116.5 microg x h x mL(-1); CL were 1.01 +/- 0.22, 0.81 +/- 0.12 and 0.89 +/- 0.08 L x h(-1) x kg(-1); V were 13.27 +/- 1.73, 12.81 +/- 2.15 and 13.28 +/- 1.20 L x 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-infinity) 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.
authors: Department of Pharmacy, Qinghai University Medical College, Xining 810001, China. qhmclxy@163.com
authors: Xiang-yang
authors: XY
authors: Li
authors: Yong-nian
authors: YN
authors: Liu
authors: Yong-ping
authors: YP
authors: Li
authors: Ming
authors: M
authors: Yuan
authors: Jun-bo
authors: JB
authors: Zhu
mesh_terms: D000328:Adult; D000531:Altitude; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People / Q000208:ethnology; D002681:China / Q000208:ethnology; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D011485:Protein Binding; D013420:Sulfamethoxazole / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D013607:Tablets; C021282:N(4)-acetylsulfamethoxazole; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D013420:Sulfamethoxazole