van der Ven A J, Schoondermark-van de Ven E M, Camps W, Melchers W J, Koopmans P P, van der Meer J W, Galama J M
Department of General Internal Medicine, University Hospital Nijmegen, The Netherlands.
J Antimicrob Chemother. 1996 Jul;38(1):75-80. doi: 10.1093/jac/38.1.75.
The aim of the present study was to determine the in-vitro susceptibility of Toxoplasma gondii to dihydrofolate reductase inhibitors and sulphonamides alone, and in combination. It was found that pyrimethamine had the most potent anti-Toxoplasma activity, while sulphadiazine, sulphamethoxazole and sulphametrole were approximately equally effective, but only at a high concentration. The 50% inhibitory concentration of sulphamethoxazole was determined using different fixed concentrations of pyrimethamine or trimethoprim. It was found that a ten-fold increment of the concentration of pyrimethamine, reduced the IC50 of sulphamethoxazole 1000 times. The influence of trimethoprim on the IC50 of sulphamethoxazole was less concentration dependent. Addition of dihydrofolate or tetrahydrofolate did not influence the IC50 of pyrimethamine. In conclusion, the present dose recommendations for sulphonamides, when combined with pyrimethamine, may be unnecessarily high. There may be a justification for dose reduction of sulphonamides in order to prevent side effects.
本研究的目的是确定弓形虫对二氢叶酸还原酶抑制剂和磺胺类药物单独及联合使用时的体外敏感性。结果发现，乙胺嘧啶具有最强的抗弓形虫活性，而磺胺嘧啶、磺胺甲恶唑和磺胺甲氧哒嗪的效果大致相同，但仅在高浓度时有效。使用不同固定浓度的乙胺嘧啶或甲氧苄啶测定了磺胺甲恶唑的50%抑制浓度。结果发现，乙胺嘧啶浓度增加10倍，磺胺甲恶唑的半数抑制浓度（IC50）降低1000倍。甲氧苄啶对磺胺甲恶唑IC50的影响与浓度的相关性较小。添加二氢叶酸或四氢叶酸对乙胺嘧啶的IC50没有影响。总之，目前磺胺类药物与乙胺嘧啶联合使用时的剂量建议可能过高。为预防副作用，降低磺胺类药物的剂量可能是合理的。
