Ribavirin Treatment of Viral Pneumonitis in Severe Combined Immunodeficiency Disease

The pharmacokinetics of ribavirin administered in single or multiple treatments to mice by small-particle aerosol were monitored in lung, serum, and brain tissues. Ribavirin aerosol was administered with a standard drug concentration (20 mg/ml) in the reservoir for 12 h or a high dose (60 mg/ml) for 2 or 4 h. After single or 3-day treatments, ribavirin rapidly accumulated in the lungs at concentrations sufficient to inhibit influenza virus or respiratory syncytial virus (1 to 5 mM). While peak levels of ribavirin in the lungs after the high-dose administration were about three times those found with the standard dose, ribavirin was rapidly cleared from the lungs. There was no accumulation of drug in the lungs after multiple treatments. Ribavirin cleared from the lungs was detected in the blood within 15 min. Concentrations in the serum were similar (20 to 30 ,IM) for standard-and high-dose treatments with either single or multiple treatments. Ribavirin clearance from the serum after treatment was similar for each regimen. Ribavirin also rapidly accumulated in the brain to a similar level (ca. 6 nmol per brain) after standard-or high-dose treatment for 3 days. In contrast to ribavirin in the serum, ribavirin in the brain appeared to be slowly cleared, allowing levels to remain relatively constant during and after treatment. With the interest in viral encephalopathies, further evaluation of the possible advantages of this method of drug administration is warranted.Ribavirin is a broad-spectrum antiviral agent that is used to treat respiratory syncytial virus infections in infants and has been shown to effectively inhibit the replication of influenza, parainfluenza, and a number of other respiratory viruses (7-10). The current protocol recommends prolonged daily ribavirin treatment periods. of 12 to 18 h. Recently, we showed that a shorter period of treatment with higher concentrations of ribavirin is as effective in reducing pulmonary viral titers in mice and cotton rats (Sigmoden hispidus) experimentally inoculated with influenza or respiratory syncytial virus and in preventing mortality in mice given lethal doses of influenza A or B virus (18,19). In the present study, the pharmacokinetics of ribavirin in lung, serum, and brain tissues of mice given standard and high doses of ribavirin by continuous small-particle aerosol were monitored by using a high-performance liquid chromatography assay (15) to determine drug levels in these tissues during and after administration. Standard administration consisted of 12 h of drug treatment per day with 20 mg of ribavirin per ml in the reservoir. High-dose, short-duration administration consisted of drug treatment for 2 h twice daily with 60 mg of ribavirin per ml in the reservoir.This report shows that after high-dose, short-duration aerosol administration, ribavirin rapidly accumulated in the lungs and was quickly cleared once treatment had ceased; that ribavirin was quickly absorbed into the blood; and that ribavirin appeared to accumulate in brain tissue. MATERIALS AND ...

Section: Methodsmentioning

confidence: 99%

“…Ribavirin is a broad-spectrum antiviral agent that is used to treat respiratory syncytial virus infections in infants and has been shown to effectively inhibit the replication of influenza, parainfluenza, and a number of other respiratory viruses (7)(8)(9)(10). The current protocol recommends prolonged daily ribavirin treatment periods.…”

mentioning

confidence: 99%

Pharmacokinetics of ribavirin aerosol in mice

Gilbert

Wyde

1988

“…Ribavirin, 1-3-D-ribofuranosyl-lH-1,2,4,-triazole-3-carboxamide, is a broad-spectrum antiviral agent that has been used successfully in small-particle aerosol to treat respiratory syncytial (2,6,10), parainfluenza (1), and influenza (3,5,7,11) virus infections of children and adults. In usual practice, ribavirin aerosols are administered for periods of 10 to 18 h/day.…”

mentioning

confidence: 99%

Protection of mice from lethal influenza virus infection with high dose-short duration ribavirin aerosol

Wyde¹,

Wilson²,

Gilbert³

et al. 1986

An aerosol generated from a reservoir containing 60 mg of ribavirin per ml given for 2 h twice daily for 4 days afforded the same high level of protection against lethal influenza virus infection of mice as a longer, conventional treatment schedule (20 mg/ml given for 11 h daily for 4 days). Incremental decreases in ribavirin concentration made while maintaining the 2-h intermittent schedule provided progressively less protection of mice. Mice exposed to the 60-mg/ml doses had significantly increased pulmonary and serum drug levels when compared with mice given 20 mg of drug per ml, these increases were transient, and no evidence of pulmonary intolerance was detected. These studies suggest that protective effects of ribavirin against influenza virus infection can be achieved without untoward effects if higher doses and shorter periods of administration are used.

“…Ribavirin, 1-3-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, a broad-spectrum antiviral agent, has been used successfully to treat respiratory syncytial virus infection in children (6,10) and respiratory syncytial virus and parainfluenza virus infections of immunodeficient children (5) by aerosol. We previously described the therapeutic efficacy of ribavirin small-particle aerosol in the treatment of influenza A/England/333/80(HlN1) virus infection in college students (7).…”

mentioning

confidence: 99%

Treatment of influenza A (H1N1) virus infection with ribavirin aerosol

Wilson¹,

Gilbert²,

Quarles³

et al. 1984

In a randomized, controlled study of ribavirin aerosol treatment of influenza A(H1N1) virus infection among college students, treated patients had a significantly shorter duration of fever than control patients. There was a trend of more rapid recovery in treated patients. Virus shedding was similar in treated and control patients, declining gradually from a 50% tissue culture infective dose of 3.5 log10 per ml at admission to 1.8 log10 per ml at 53 h after admission. There was no local or systemic intolerance and no hematological or biochemical abnormalities associated with ribavirin treatment.