Seydel J K, Wempe E
Arzneimittelforschung. 1977;27(8):1521-32.
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.
根据细菌生长动力学研究结果,使用相当低浓度的磺胺类药物(SA)就能获得磺胺类药物(SA)-甲氧苄啶(TMP)组合对大肠杆菌的最大可能抑制作用。在这些研究中,TMP浓度(显著低于血浆最低水平)保持恒定,SA浓度则有所变化。已观察到高浓度SA对该组合协同效应具有“拮抗”作用,并降低了TMP的抑制作用。根据用大肠杆菌进行的细菌生长动力学结果以及所呈现的药代动力学研究,2-磺胺-4,5-二甲基恶唑/TMP组合的建议剂量似乎足够,给药方案正确,而在磺胺甲恶唑(SMZ)/TMP组合建议剂量中3-磺胺-5-甲基异恶唑(SMZ)的量似乎过高且给药方案不正确。