Epstein L J, Mohsenifar Z, Daar E S, Yeh V, Meyer R D
Division of Pulmonary and Critical Care Medicine, Wilford Hall Medical Center, Lackland Air Force Base, San Antonio, Texas.
Am J Med Sci. 1994 Jul;308(1):5-8. doi: 10.1097/00000441-199407000-00003.
Atovaquone is a new hydroxynapthoquinone antiprotozoal agent active against Pneumocystis carinii in vitro and in animal models. The authors report an experience using atovaquone to treat 25 patients with mild to moderate P. carinii pneumonia. Eligible patients were treated for 21 days with 750 mg of atovaquone orally three times daily. Prednisone was added when the P(A-a)O2 gradient was between 35-45 mm Hg. Patients were treated under three treatment protocols. Patients in Group 1 participated in one of two randomized comparative drug trials, designed for patients with and without sulfonamide intolerance. Six of seven patients successfully completed treatment, and one patient discontinued treatment because of an adverse reaction (> 5 times baseline increase in transaminase level). Patients in Group 2 were treated with atovaquone for mild to moderate P. carinii pneumonia under a treatment Investigational New Drug protocol because of prior sulfonamide reactions. Fifteen of these 18 patients successfully completed treatment; one died from other complications during treatment and two discontinued treatment for adverse reactions (> 5 times baseline increase in transaminase levels, and a diffuse rash). Serum transaminase levels returned to normal at the end of treatment in all patients with elevated levels. All patients demonstrated clinical resolution of their pneumonia and improvement of pretreatment hypoxemia (Group 1: pretreatment PaO2 = 82 +/- 14 mm Hg, posttreatment PaO2 = 92 +/- 9 mm Hg). Overall, 21 (84%) of 25 patients successfully finished therapy without significant adverse reactions. Atovaquone appears to be an effective and well-tolerated oral treatment for mild to moderate P. carinii pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)
阿托伐醌是一种新型羟基萘醌类抗寄生虫药,在体外和动物模型中对卡氏肺孢子虫具有活性。作者报告了使用阿托伐醌治疗25例轻至中度卡氏肺孢子虫肺炎患者的经验。符合条件的患者接受为期21天的治疗,口服阿托伐醌750毫克,每日三次。当动脉血氧分压差(P(A-a)O2)在35 - 45毫米汞柱之间时加用泼尼松。患者按照三种治疗方案进行治疗。第1组患者参与了两项随机对照药物试验之一,试验针对有或无磺胺类药物不耐受的患者设计。7例患者中有6例成功完成治疗,1例因不良反应(转氨酶水平升高超过基线5倍)而停止治疗。第2组患者因先前的磺胺类药物反应,根据治疗用新药研究方案,使用阿托伐醌治疗轻至中度卡氏肺孢子虫肺炎。这18例患者中有15例成功完成治疗;1例在治疗期间死于其他并发症,2例因不良反应(转氨酶水平升高超过基线5倍,以及弥漫性皮疹)而停止治疗。所有转氨酶水平升高的患者在治疗结束时血清转氨酶水平恢复正常。所有患者的肺炎均有临床缓解,治疗前的低氧血症有所改善(第1组:治疗前动脉血氧分压(PaO2)= 82±14毫米汞柱,治疗后PaO2 = 92±9毫米汞柱)。总体而言,25例患者中有21例(84%)成功完成治疗,且无明显不良反应。阿托伐醌似乎是治疗轻至中度卡氏肺孢子虫肺炎的一种有效且耐受性良好的口服药物。(摘要截选至250字)