title: Steady state pharmacokinetics of trimethoprim 300 mg once daily in healthy volunteers assessed by two independent methods.
abstract: The steady state pharmacokinetics of trimethoprim was determined after 300 mg orally once daily to 6 healthy volunteers for 9 days. The microbiological assay of plasma level was unreliable at trimethoprim concentrations greater than 4 micrograms/ml, so results from an HPLC-assay are given. Steady state was present after 3 days. The plasma concentration peaked 1 to 4 h (mean 2.0 h) after the dose at a mean of 6.0 micrograms/ml (range 3.1-9.5 micrograms/ml); the minimum value was 1.5 micrograms/ml (range 0.6-2.9 micrograms/ml). The mean AUCss was 77 micrograms/ml X h and the mean plasma clearances was 67 and 74 ml/min on Days 8 and 9. Renal clearance was about 60% of the plasma clearance. The average plasma half life was 10.6 h (range 8.7-15.3 h). Thus, there was considerable interindividual variation in all pharmacokinetic parameters. 72 h after the last dose trimethoprim was detectable in plasma in only 1 of the 6 subjects. The minimum urinary concentration of trimethoprim during treatment was always well above (range 22 to 220 micrograms/ml) the MIC values for most urinary tract pathogens. Therefore, a daily dose of 300 mg trimethoprim results in a therapeutic concentration in urine at steady state that lasts throughout the dosing interval and in most subjects probably lasts also for a further 24 h. Trimethoprim administration raised mean serum creatinine from 67 to 97 mumol/l, probably due to competitive inhibition of the tubular secretion of creatinine.
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D014295:Trimethoprim / Q000097:blood / Q000378:metabolism*
chemical_list: D014295:Trimethoprim; D003404:Creatinine