The inhibitory quotient (IQ) is defined herein as the ratio of the expected average total (free and protein-bound) plasma concentration (C ave ) of each drug at recommended dosage to the EC 50 (C ave /EC 50 ). Thus, an IQ of 1 or greater means that the achievable total plasma concentration of the drug is equal to or greater than the in vitro 50% effective concentration, and the higher the IQ translates to a greater predicted efficacy. The C ave of each drug was determined by pharmacokinetic modeling using a non-compartmental model in the progam WinNonLin. The recommended doses, along with the pharmacokinetic parameters, used for modeling were obtained from the package inserts for amantadine [14] , oseltamivir [15] , and ribavirin [16] , and the references therein. For ribavirin, since the plasma concentration does not achieve steady-state until ,4 weeks after the start of dosing, the C ave was determined for the first 10-day window. Based on these parameters, the expected C ave for amantadine was determined to be 0.43 mg/mL based on the recommended dosage of 100 mg twice daily for the treatment of influenza infection; the expected C ave for oseltamivir was determined to be 0.3 mg/mL based on the recommended dosage of 75 mg twice daily for the treatment of influenza infection; and the expected C ave of for ribavirin was determined to be 1.3 mg/mL after 10 days of treatment based on the recommended dosage of 600 mg twice daily for the treatment of hepatitis C infection. To determine the IQ of the triple combination, amantadine, ribavirin, and oseltamivir carboxylate were tested as a fixed ratio combination, wherein the ratio of the three drugs was kept constant even as the total concentration of drugs varied. The ratio of drugs in the TCAD regimen was based on the expected C ave of each drug. A dilution curve of TCAD regimen was created by first preparing a solution of all three drugs at 100-fold the C ave of each drug (43 mg/ mL amantadine, 30 mg/mL oseltamivir carboxylate, and 130 mg/ mL ribavirin), and then serially diluting this solution in 0.5-log 10 increments. In this manner, the EC 50 of TCAD regimen as a fixed dose combination was determined as ratio of the C ave and expressed in units of fold-C ave .