Pharmacokinetics of Trimethoprim and its Combination with Sulfamethoxazole in Man after Single and Chronic Oral Administration

Abstract

Trimethoprim is absorbed well in man. Plasma peak levels between 0.9 and 1.9 μg/ml are reached within 2–4 h after ingestion of 160 mg TMP alone or in combination with 800 mg SMZ. Plasma disappearance of TMP is characterized by first order processes. Elimination half-lives range between 6 and 17 h. Assuming total absorption the apparent volume of distribution for TMP is approximately 1001. Urine recovery of TMP after single oral administration is 75% of the administered dose. Pharmacokinetics of TMP after single oral application are not altered by simultaneous administration of SMZ. Steady-state plasma levels of almost always 1.2–1.7 μg/ ml are achieved after 2–3 days and maintained on a chronic oral dosing schedule of 160 mg TMP every 12 h. The recovery of intact TMP in the urine during chronic administration is approximately 50% for all subjects studied. Simultaneous application of SMZ in the repetitive dosing study does not change the pharmacokinetics of TMP. Peak plasma levels after single oral administration correspond to plateau concentrations during chronic oral application of TMP.