二氢叶酸还原酶的脂溶性抑制剂在体外培养及大鼠感染模型中对卡氏肺孢子虫的活性
Activity of lipid-soluble inhibitors of dihydrofolate reductase against Pneumocystis carinii in culture and in a rat model of infection.
作者信息
Queener S F, Bartlett M S, Jay M A, Durkin M M, Smith J W
机构信息
Department of Pharmacology, Indiana University School of Medicine, Indianapolis 46223.
出版信息
Antimicrob Agents Chemother. 1987 Sep;31(9):1323-7. doi: 10.1128/AAC.31.9.1323.
Abstract
Trimetrexate and BW301U (piritrexim isethionate), lipid-soluble inhibitors of dihydrofolate reductase, are potent inhibitors of the growth of Pneumocystis carinii in culture with WI-38 cells. Inhibition was observed with 0.1 microgram of trimetrexate or BW301U per ml. Trimethoprim is ineffective at 100 micrograms/ml in this culture system. Both trimetrexate and BW301U were effective as prophylactic agents against P. carinii pneumonia in rats; trimetrexate at 7.5 mg/kg protected 9 of 10 rats, and BW301U at 5 mg/kg protected 4 of 10.
摘要
三甲曲沙和BW301U（吡曲克辛羟乙磺酸盐）是二氢叶酸还原酶的脂溶性抑制剂，在与WI-38细胞共培养时，它们是卡氏肺孢子虫生长的强效抑制剂。每毫升含0.1微克三甲曲沙或BW301U时即可观察到抑制作用。在该培养系统中，甲氧苄啶在100微克/毫升时无效。三甲曲沙和BW301U作为大鼠卡氏肺孢子虫肺炎的预防药物均有效；7.5毫克/千克的三甲曲沙保护了10只大鼠中的9只，5毫克/千克的BW301U保护了10只大鼠中的4只。
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