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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Serum and saliva concentrations of sulfamethoxazole and trimethoprim in adults and children: relation between saliva concentrations and in vitro activity against nasopharyngeal pathogens.

The combination sulfamethoxazole/trimethoprim (SMX/TMP) was given orally to 4 healthy adult volunteers in mean daily doses of 23.0/4.6 mg/kg body weight for 6 days. The serum and saliva concentrations of the drugs were assayed on days 1, 3 and 6. On the first day (0-12 h) there was no measurable concentration of SMX in the saliva. On days 3 and 6 the mean peak levels of SMX in saliva were 7.8 and 9.8 micrograms/ml, i.e. 8-9% of the corresponding mean peak serum levels. In contrast, the concentrations of TMP in saliva were more than twice as high as those in serum. The mean SMX/TMP ratios in saliva days 3 and 6 were 1.3 and 1.4, respectively, i.e. approximately one-twentieth of the mean SMX/TMP ratios in serum. SMX/TMP was also administered to children with serous otitis media. The drug concentrations in saliva were assayed 2-3 h after administration on days 6 and 9 of a 10-day course, with a mean daily dose of 34.5/6.9 mg/kg body weight. The mean saliva concentration of SMX in the children was slightly higher than in adults and the mean TMP concentration about half of that in adults. The mean SMX/TMP ratio in the children's saliva was 4. 2. The in vitro activity of SMX/TMP 20:1 and 4:1 was determined against H. influenzae, D. pneumoniae, B. catarrhalis and group A streptococci. H. influenzae, D. pneumoniae and group A streptococci were found more susceptible to TMP than to SMX, while the reverse was true for B. catarrhalis. In the 3 former, the potentiation of SMX by TMP was more pronounced than was the potentiation of TMP by SMX, while the opposite was recorded for B. catarrhalis. The most beneficial effect of the SMX/TMP combination against nasopharyngeal pathogens was recorded for B. catarrhalis and the weakest effect for H. influenzae and group A streptococci. With the exception of B. catarrhalis, the administration of TMP alone to adults may be just as effective against nasopharyngeal pathogens as is the SMX/TMP combination in children.[1]


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