Gilbert B E, Wyde P R, Ambrose M W, Wilson S Z, Knight V
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030.
Antiviral Res. 1992 Jan;17(1):33-42. doi: 10.1016/0166-3542(92)90088-m.
Ribavirin aerosol administration has been shown to be effective in the treatment of respiratory syncytial virus (RSV) infections in infants and in influenza A and B virus infections in young adults. Long treatment schedules and potential for environmental contamination have stimulated the search for alternative dosing schedules. Thus, we attempted to determine the length of time of ribavirin aerosol necessary for effective treatment of influenza and RSV. In RSV-infected cotton rats, aerosolization for just 30 min with high-dose ribavirin (HDR:60 mg ribavirin/ml in reservoir), 3 times daily, reduced viral lung titers/gm of tissue by 1.1 log10. In influenza virus-infected mice, 15 min of aerosolized HDR, 3 times daily, was effective in reducing both mortality and pulmonary virus titers (1.1 log10 reduction). When the intervals between aerosol administration each day were equally divided (i.e., q.8 h), the treatments were most effective. Treatment for 45 min, once daily, was not as effective as divided doses. Calculations of ribavirin concentrations in respiratory secretions following 15 min treatment in mice with HDR indicated that drug levels dropped below the ED50 for influenza viruses after about 9 h. A daily dosage of ribavirin, estimated to be 8-15 mg/kg, was effective for the treatment of influenza and RSV infections.
已证明雾化吸入利巴韦林对治疗婴儿呼吸道合胞病毒（RSV）感染以及青年成人甲型和乙型流感病毒感染有效。长期的治疗方案以及可能造成环境污染促使人们寻找其他给药方案。因此，我们试图确定有效治疗流感和RSV所需的利巴韦林雾化时间。在感染RSV的棉鼠中，每天3次用高剂量利巴韦林（HDR：储液器中60mg利巴韦林/ ml）雾化仅30分钟，可使每克组织的病毒肺滴度降低1.1 log10。在感染流感病毒的小鼠中，每天3次雾化HDR 15分钟可有效降低死亡率和肺病毒滴度（降低1.1 log10）。当每天雾化给药的间隔时间平均分配（即每8小时一次）时，治疗效果最佳。每天治疗一次45分钟不如分次给药有效。对感染HDR的小鼠进行15分钟治疗后，呼吸道分泌物中利巴韦林浓度的计算表明，约9小时后药物水平降至流感病毒的ED50以下。估计每日剂量为8 - 15mg / kg的利巴韦林对治疗流感和RSV感染有效。
