TABLE 1.
Parameter values and dispersions from the mathematical model fitted to murine PK-PD data
| Parametera | Value |
||
|---|---|---|---|
| Mean | Median | SD | |
| Ka (h−1) | 0.974 | 0.974 | 0.052 |
| SCL/F (liters/h) | 0.006 | 0.006 | 0.000 |
| V/F (liters) | 0.008 | 0.008 | 0.001 |
| Kcp (h−1) | 2.391 | 2.391 | 0.026 |
| Kpc (h−1) | 15.667 | 15.667 | 4.741 |
| Kcs (h−1) | 18.853 | 18.853 | 5.959 |
| Ksc (h−1) | 11.872 | 11.872 | 1.736 |
| Vcns/f (liters) | 0.024 | 0.024 | 0.009 |
| Kgmax_s (log10 CFU/g/h) | 0.078 | 0.080 | 0.014 |
| popmax (CFU/g) | 26,294,350.171 | 42,296,494.976 | 22,574,600.414 |
| kkmax_s (log10 CFU/g/h) | 0.257 | 0.279 | 0.022 |
| C50k_s (mg/liter) | 25.090 | 23.496 | 1.641 |
| Hk_s | 15.252 | 14.323 | 1.167 |
| Kgmax_r (log10 CFU/g/h) | 0.032 | 0.026 | 0.007 |
| kkmax_r (log10 CFU/g/h) | 1.469 | 1.716 | 0.436 |
| C50k_r (mg/liter) | 88.795 | 89.265 | 1.809 |
| Hk_r | 18.989 | 19.822 | 0.950 |
| IC_s (CFU/g) | 148.570 | 144.106 | 17.730 |
| IC_r (CFU/g) | 9.230 | 10.000 | 1.493 |
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.