The incidence of adverse reactions frequency to cotrimoxazole (mixture of sulfamethoxazole SMX, a sulphonamide and trimethoprim) is much higher in HIV-seropositive individuals (6-80%) as compared with seronegative individuals (<5%). This toxicity increase has been linked with sulphonamide hydroxylamine metabolites production. In fact, SMX metabolism leads to N-acethylsulfamethoxazole (ASMX) by acetylation (80%) and to hydroxysulfamethoxazole (OXSMX) by oxidation (CYP 1A2). We present here some preliminary results of urinary and blood pharmacokinetic parameters after 400 mg oral doses of SMX given during 5 days in 13 healthy volunteers. At the same time we have studied acetylation and oxidative (CYP 1A2) metabolism of each volunteer using urinary caffeine metabolite ratios before SMX treatment, and on the 5th day of SMX treatment.We found that SMX half life elimination was significantly longer (p=0.01 Mann-Whitney test) in slow acetylator group than in fast acetylator group as determined by caffeine probe. On the other hand we haven't found any correlation between acetylator status and urinary ASMX and SMX ratio. This is probably due to the high SMX urinary elimination variability (10 to 60%) and greatly correlated with diuresis and urinary pH (p<0.001 Spearman test). No correlation were found between ASMX urinary metabolites and SMX, OXSMX, diuresis, urinary pH. Furthermore we haven't found any correlation between metabolic ratios of CYP 1A2 and OXSMX urinary metabolites, probably because of small OXSMX eliminated amount (<5% total amount), the small studied population, and the correlation between OXSMX elimination and diuresis (p=0.04) as well as the SMX eliminated amount (p<0.02) but not with urinary pH and ASMX eliminated amount.In conclusion, these preliminary data have confirmed the significance of metabolic status in SMX elimination while permitting a better understanding of the variables which may influence SMX metabolism, and therefore toxicity.