Kovacs J A, Allegra C J, Kennedy S, Swan J C, Drake J, Parrillo J E, Chabner B, Masur H
Critical Care Medicine Department, National Cancer Institute, Bethesda, Maryland 20892.
Am J Trop Med Hyg. 1988 Nov;39(5):491-6. doi: 10.4269/ajtmh.1988.39.491.
Trimetrexate is a lipid-soluble antifolate that has been shown in vitro to be a much more potent inhibitor of Pneumocystis carinii dihydrofolate reductase than the conventionally used inhibitor trimethoprim. To evaluate the in vivo efficacy of trimetrexate, steroid-treated rats which spontaneously develop P. carinii pneumonia were used. Rats treated with trimetrexate (25 mg/kg/d) plus sulfamethoxazole (250 mg/kg/d) orally responded at least as well as rats treated with trimethoprim (50 mg/kg/d) plus sulfamethoxazole. Trimetrexate alone administered orally was ineffective in treating P. carinii infection, but subcutaneous (sc) trimetrexate (7 mg/kg/d) significantly decreased the intensity of infection compared to controls. Trimetrexate is a potent antifolate that may provide an effective alternative to pentamidine and trimethoprim-sulfamethoxazole for treatment of P. carinii pneumonia in humans.
三甲曲沙是一种脂溶性抗叶酸剂，体外实验表明，它对卡氏肺孢子虫二氢叶酸还原酶的抑制作用比传统使用的抑制剂甲氧苄啶强得多。为评估三甲曲沙的体内疗效，研究人员使用了经类固醇处理后自发感染卡氏肺孢子虫肺炎的大鼠。口服三甲曲沙（25毫克/千克/天）加磺胺甲恶唑（250毫克/千克/天）的大鼠，其反应至少与口服甲氧苄啶（50毫克/千克/天）加磺胺甲恶唑的大鼠相同。单独口服三甲曲沙对治疗卡氏肺孢子虫感染无效，但皮下注射三甲曲沙（7毫克/千克/天）与对照组相比，显著降低了感染强度。三甲曲沙是一种强效抗叶酸剂，可能为人类治疗卡氏肺孢子虫肺炎提供一种有效的替代喷他脒和甲氧苄啶 - 磺胺甲恶唑的药物。
