Pharmacokinetics of trimethoprim in the rat

The pharmacokinetics of trimethoprim was studied in male Sprague-Dawley rats following the intravenous administration of trimethoprim at a dose of 25 mg/kg. Plasma and tissue levels of trimethoprim, as a function of time, were determined by reversed-phase high-performance liquid chromatography. The disposition of trimethoprim was described by both a two-compartment open model with elimination from a central compartment and a noncompartmental method. For the compartmental analysis, the terminal elimination rate constant, elimination half-life, apparent volume of distribution in the central compartment, apparent volume of distribution in the central compartment based on the area under the plasma concentration-time curve, and volume of distribution at steady state, were determined to be 0.007 min-1, 99 min, 2059 mL/kg, 5729 mL/kg, and 2473 mL/kg, respectively. Noncompartmental pharmacokinetic parameters were obtained by the statistical moment theory. The estimates for mean residence time, clearance, and volume of distribution at steady state of trimethoprim were calculated to be 52 min, 40 mL.min-1kg-1, and 2097 mL, respectively. Tissue distribution of trimethoprim followed a biphasic phenomenon with a maximum concentration at 30 min for heart, lung, spleen, liver, kidney, seminal vesicles, and muscle, and at 45 min for testicles, 20 min for prostate gland, and less than 10 min for brain. The data show that compared with the plasma concentration, higher levels of trimethoprim were found in heart, lung, spleen, liver, kidney, prostate gland, and seminal vesicles; a similar concentration was found for muscle, but lower levels of trimethoprim were found for brain and testicles.