Absorption and Urinary Execretion of Trimethoprim, Sulfamethoxazole, and Trimethoprim-Sulfamethoxazole: Results with Single Doses in Normal Young Adults and Preliminary Observations during Therapy with Trimethoprim-Sulfamethoxazole

Abstract

Crossover studies of absorption and excretion of single oral doses of trimethoprim (TMP), sulfamethoxazole (SMZ) and the combination (TMP-SMZ) were done in 18 normal young adults. Each received 100 mg of TMP, 500 mg of SMZ, and 480 mg of TMP-SMZ (80 mg of TMP + 400 mg of SMZ) in Latin square rotation, and groups of six received a single dose of twice these amounts. Levels of TMP in serum and of SMZ in oxalated blood varied widely at each interval but were roughly proportional to the administered amounts. From 50% to 60% of the dose of TMP and one fourth to one half of the dose of SMZ was recovered in the urine in 24 hr; nearly two thirds of the latter was unconjugated. Concentrations of TMP and SMZ in blood of patients treated with TMP-SMZ corresponded to those expected from the findings in the normal subjects. The ratio of TMP to SMZ in blood increased with time from 1:30, and in urine from 1:3 to ⩾ 1:5. High concentrations of TMP and SMZ were demonstrated in sputum and in pleural and cerebrospinal fluids. TMP was equally distributed between plasma and erythrocytes, but the concentration of SMZ was much higher in plasma.