Studies on Sulfamethoxazole/Trimethoprim: Absorption, Distribution, Excretion and Metabolism of Trimethoprim in Rat

Abstract

Absorption, distribution, excretion and metabolism of trimethoprim were studied in rats. Trimethoprim was absorbed rapidly and almost completely from the digestive tract, the half-life for absorption being 18 min. After absorption the drug left the blood rapidly and was taken up by various organs except brain. The highest concentration was found in the kidney. Appreciable levels were found in the bone marrow, thyroid, liver and lung. The lowest drug concentration was noted in the brain. Approximately 95 % of the radioactivity after oral administration of 14C-trimethoprim was recovered from the urine and feces within 72 hr. The urinary excretion is the major excretory route since more than 85% of the total radioactivity recovered appeared in the 72 hr urine. About 30% of the radioactivity excerted in 8 hr urine was present as intact 14C-trimethoprim. Metabolic pathways of trimethoprim consisted of O-demethylation, ring N-oxidation and α-hydroxylation. 3-Demethyl-trimethoprim was the largest metabolite which accounted for more than 30% of the radioactivity excreted in 8 hr urine. 4-Demethyl-trimethoprim was excerted mainly as glucuronide which accounted for about 19%. Tri-methoprim ring N-oxide and a-hydroxy-trimethoprim were excreted in amounts of 7 and 5%, respectively. Simultaneous administration of sulfamethoxazole did not influence the absorption, distribution, excretion and metabolism of trimethoprim in rat. © 1972, The Pharmaceutical Society of Japan. All rights reserved.