[Studies on synergistic behaviour and pharmacokinetics of the combination sulfonamide/trimethoprim. IV. A comparative study on potentiating the trimethoprim effect by various sulfonamides and critical observations on its dosing (author's transl)].

1977; National Institutes of Health; Volume: 27; Issue: 8 Linguagem: Inglês

Autores

Seydel Jk, Ellen Wempe,

Tópico(s)

Pharmacogenetics and Drug Metabolism

Resumo

The maximum possible inhibitory effect of sulfonamide-(SA)-trimethoprim (TMP) combinations on E. coli is obtained with rather small concentrations of SA according to the results obtained with bacterial growth kinetic studies. In these studies the TMP concentration (significantly below the minimum plasma level) was kept constant and the SA concentration varied. An "antagonistic" effect of high SA concentrations on the synergistic effect of the combination and a reduction of the inhibitory effect of TMP has been observed. According to the results of the bacterial growth kinetics obtained with E. coli and pharmacokinetic studies presented, the suggested dose for the combination 2-sulfa-4,5-dimethyl-oxazole/TMP seems to be sufficient, the dosage regimen is correct, whereas the amount of 3-sulfa-5-methyl-isoxazole (SMZ) in the dose proposed for the combination SMZ/TMP seems to be unreasonably high and the dosage scheme is incorrect.

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