TABLE 1

Parameter values and dispersions from the mathematical model fitted to murine PK-PD data

• a Parameters are as follows: Ka is the first-order rate constant that connects the gut to the bloodstream; SCL is the first-order clearance of fluconazole from the central compartment (i.e., bloodstream); V is the volume of the central compartment; Kcp and Kpc are the first-order intercompartmental rate constants that connect the central and peripheral compartments; Ksc and Kcs are the first-order intercompartmental rate constants that connect the central compartment and CSF; Vcns is the volume of the CSF; F is the oral bioavailability of fluconazole; Kgmax_s and Kgmax_r are the maximum growth rates of the susceptible and resistant subpopulations, respectively; popmax is the maximum theoretical fungal density in the cerebrum; kkmax_s is the maximum rate of fluconazole killing of the susceptible subpopulation in the cerebrum; C50k_s is the cerebral concentration of fluconazole at which the rate of killing of the susceptible subpopulation is half maximal; Hk_s is the slope function for the effect of fluconazole on the susceptible population; kkmax_r is the maximum rate of fluconazole killing of the resistant subpopulation in the cerebrum; C50k_r is the cerebral concentration of fluconazole at which the rate of killing of the resistant subpopulation is half maximal; Hk_r is the slope function for the effect of fluconazole on the resistant population; and IC_s and IC_r are the estimated initial densities of the susceptible and resistant subpopulations in the cerebrum, respectively.