Synchronous Dynamics of Observed and Predicted Values of Anti-influenza drugs in Environmental Waters during a Seasonal Influenza Outbreak

Time-dependent dynamics in the concentrations of four anti-influenza drugs (oseltamivir, oseltamivir carboxylate, zanamivir, and amantadine) in environmental waters collected from the Yodo River basin, Japan, were monitored for the first time over a 1 year period (July 2010 to June 2011). The clear, convex dynamic profiles of oseltamivir, oseltamivir carboxylate, and zanamivir during a 3 month seasonal influenza outbreak (January to March 2011) were synchronized well with that of the numbers of influenza patients treated with the drugs. The highest levels in sewage treatment plants (STPs) and river waters were, respectively, 177 and 60 ng/L (oseltamivir), 827 and 288 ng/L (oseltamivir carboxylate), and 30 and 15 ng/L (zanamivir). Fixed levels of amantadine were detectable year-round (100-200 ng/L in the STPs and 10-30 ng/L in river waters). The predicted convex profiles of oseltamivir, oseltamivir carboxylate, and zanamivir in both STPs and river waters were significantly correlated (0.714 < R < 0.932) with the observed values. The profiles were predicted successfully by simple mathematical principles, taking the number of influenza patients, quantities of Tamiflu and Relenza used, dilution by drainwaters passing through STPs, removal rates at STPs, dilution rates in river effluents, and attenuation rates in rivers into consideration.