Trimethoprim in Normal and Pathological Human Lung Tissue

Abstract

Following oral administration of trimethoprim (TMP) in doses varying from 5.7 to 9.8 mg TMP per kg body weight per 24 h over a period of 1–22 days, the concentration was determined in normal and pathological lung Concentration tissue (obtained by open biopsy) in a total of 45 cases. A microbiological method was used to determine the concentration, using Bacillus pumilus as test organism. The concentration of TMP in lung tissue was found to be significantly higher than in serum. The increased concentration in macroscopically normal lung tissue varied from 1 to 8½ times the corresponding serum concentration (the median ratio = 3½), and was found to be independent of the magnitude of the dose administered, the duration of the administration and the pathological changes in the lung tissue when evaluated by histological examination. In lung tissue with a macroscopical appearance of inflammation or atelectasis, a significantly higher TMP concentration was found than in tissue with a normal appearance. The concentration of TMP varied from 2 to 12½ times the corresponding serum concentration (the median ratio = 5).