Abstract: AIM:To investigate the effect of compound sulfamethoxazole on the rosiglitazone pharmacokinetics in normal Chinese subjects and assess the safety when they are coadministrated in clinic. METHODS: Ten male healthy volunteers completed a randomized, two-period, double-blind crossover study. Volunteers received single dose rosiglitazone (4 mg)in the presence and absence of compound sulfamethoxazole 1g given twice daily for 4. 5 days. The plasma drug concentrations were determined at each time point after oral rosiglitazone. The related pharmacokinetical parameters in vivo were computed. The concentrations of rosiglitazone and N-demethylrosiglitazone were assessed by HPLC-MS/MS. RESULTS:The C_max and t_maxof rosiglitazone and N-demethylrosiglitazone were not changed by compound sulfamethoxazole treatment, respectively(P >0. 05).But the AUC_0-48 of rosiglitazone was increased by 40% (P =0. 000)from (6768 ±900)ng·mL^-1·h to (9485 ±1638)ng·mL^-1·h, and the t_maxwas increased by 44% (P =0. 007)from (4. 4 ±0. 8)to (6. 1 ±1. 2)h. The AUC_0-48 of biotransformation rate of N-demethylrosiglitazone/rosiglitazone was decreased to 59. 8% (P =0. 001).CONCLUSION: Compound sulfamethoxazole decreases the rosiglitazone biotransformation rate and increases the plasma rosiglitazone concentrations in healthy volunteers when they are co-administrated.

Key words: compound sulfamethoxazole, rosiglitazone, pharmacokinetical parameters, HPLC-MS/MS