Englund J A, Piedra P A, Jefferson L S, Wilson S Z, Taber L H, Gilbert B E
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030.
J Pediatr. 1990 Aug;117(2 Pt 1):313-20. doi: 10.1016/s0022-3476(05)80554-2.
Nine children (aged 6 weeks to 7 years) with suspected respiratory syncytial virus infection received aerosal treatment with ribavirin, 60 mg/ml for 2-hour periods three times daily for up to 5 days. Five children received treatment via an endotracheal tube and four via an oxygen hood. Blood samples (3 to 17 per patient) and respiratory secretions (4 to 23 per patient) were assayed for ribavirin with reverse-phase high-performance liquid chromatography. Ribavirin triphosphate in erythrocytes was determined by ion-exchange high-performance liquid chromatography. The mean (+/- SD) peak ribavirin level after the first dose was 1725 +/- 2179 mumol/L in secretions and 3.8 +/- 2.6 mumol/L in plasma. Ribavirin in the secretions was rapidly cleared, with a mean (+/- SD), half-life of 1.9 +/- 0.8 hours. Plasma ribavirin increased with treatments to reach a steady state of 5 to 10 mumol/L. Mean peak ribavirin triphosphate levels were 15- to 300-fold higher than plasma ribavirin levels by the end of therapy. More than 98% reduction of viral load without the emergence of resistant virus was noted on day 3 of therapy. High-dose treatment was compatible with the aerosol equipment routinely used (small-particle aerosol generator, model 2-6000) for ribavirin administration and with ventilators. High-dose, short-duration ribavirin therapy was well tolerated by all patients, permitted easier accessibility for patient care, and may result in less environmental exposure of health care workers.
9名疑似感染呼吸道合胞病毒的儿童（年龄6周至7岁）接受了利巴韦林雾化治疗，剂量为60mg/ml，每日3次，每次2小时，持续5天。5名儿童通过气管内插管接受治疗，4名通过氧气面罩接受治疗。采用反相高效液相色谱法对血样（每名患者3至17份）和呼吸道分泌物（每名患者4至23份）进行利巴韦林检测。采用离子交换高效液相色谱法测定红细胞中的三磷酸利巴韦林。首剂后，分泌物中利巴韦林的平均（±标准差）峰值水平为1725±2179μmol/L，血浆中为3.8±2.6μmol/L。分泌物中的利巴韦林迅速清除，平均（±标准差）半衰期为1.9±0.8小时。血浆利巴韦林水平随治疗增加，达到5至10μmol/L的稳态。治疗结束时，三磷酸利巴韦林的平均峰值水平比血浆利巴韦林水平高15至300倍。治疗第3天，病毒载量降低超过98%，且未出现耐药病毒。高剂量治疗与常规用于利巴韦林给药的雾化设备（2-6000型小颗粒雾化发生器）和呼吸机兼容。所有患者对高剂量、短疗程利巴韦林治疗耐受性良好，便于患者护理，且可能减少医护人员的环境暴露。
