Steady-state pharmacokinetics of sulfamethoxazole and trimethorprim in man after rectal application

The pharmacokinetics of a combination of 800 mg sulfamethoxazole (SMZ) and 160 mg trimethoprim (TMP) were studied in 5 healthy male volunteers after repetitive rectal administration at constant 8-h dosing intervals. The average serum concentrations measured in steady-state between the fourth and seventh days showed a range for total SMZ of 47.86 to 63.38 microgram/ml. Free SMZ was between 40.04 and 51.42 microgram/ml and TMP between 1.44 and 2.20 microgram/ml. The ratio of total SMZ to free SMZ did not change during the course of the investigation. The pharmacokinetic parameters were derived from a simultaneous curve fitting of the Bateman function on the basis of the multiple dose equation. The values thus found for V0 and t50% correlate essentially with those found in the literature for oral administration. In addition, the final serum minimums and maximums were calculated. Extrapolation from t leads to infinity gave a serum minimum for total SMZ of 51.7 microgram/ml and 1.8 microgram/ml for TMP. The course of the curve fitting did not show an accumulative trend so that, in fact, it can be assumed that a steady-state was present.