Abstract
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 microM) 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.
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