Masur H, Polis M A, Tuazon C U, Ogata-Arakaki D, Kovacs J A, Katz D, Hilt D, Simmons T, Feuerstein I, Lundgren B
National Institutes of Health, Bethesda, MD 20892.
J Infect Dis. 1993 Jun;167(6):1422-6. doi: 10.1093/infdis/167.6.1422.
The clinical efficacy of trimetrexate, a dihydrofolate reductase inhibitor with potent in vitro antitoxoplasma activity, was assessed in 9 sulfonamide-intolerant patients with AIDS and biopsy-proven cerebral toxoplasmosis. The 9 patients were treated for 28-149 days with trimetrexate (30-280 mg/m2/day) plus leucovorin (20-90 mg/m2 every 6 h). Radiographic responses were documented in 8 patients, and clinical responses in 5 patients. Despite continued therapy, all patients deteriorated clinically and radiographically within 13-109 days of their initial improvement. Trimetrexate at very high doses for extended periods was not associated with serious toxicity. Trimetrexate alone had dramatic but transient activity in sulfonamide-intolerant patients and thus is not adequate as single-agent therapy for AIDS-associated toxoplasmosis.
三甲曲沙是一种二氢叶酸还原酶抑制剂，具有强大的体外抗弓形虫活性。我们评估了其对9名不耐受磺胺类药物且经活检证实患有脑弓形虫病的艾滋病患者的临床疗效。这9名患者接受了28至149天的三甲曲沙（30至280毫克/平方米/天）加亚叶酸（每6小时20至90毫克/平方米）治疗。8名患者有影像学反应，5名患者有临床反应。尽管持续治疗，但所有患者在初次改善后的13至109天内临床和影像学均出现恶化。长时间使用极高剂量的三甲曲沙并未出现严重毒性。三甲曲沙单独使用时，对不耐受磺胺类药物的患者有显著但短暂的活性，因此作为艾滋病相关弓形虫病的单药治疗并不充分。
