A strategy for designing voriconazole dosage regimens to prevent invasive pulmonary aspergillosis based on a cellular pharmacokinetics/pharmacodynamics model

Table 1 The regression parameters and statistical analysis of the extracellular concentrations-activity curves illustrated in Fig. 2

Strain	E_max (95%CI)^a	E_min (95%CI)^b	EC₅₀ (95%CI)^c	C ^d_s	R^2e
AF293	− 0.79 (− 0.86 ~ − 0.72) lg cfu	0.21 (0.18 ~ 0.24) lg cfu	7.05 mg/L (5.36 ~ 9.27) 36.71 × MIC (27.91 ~ 48.30)	1.86 mg/L (9.69 × MIC)	0.9813
AF26	− 0.84 (− 0.89 ~ − 0.78) lg cfu	0.20 (0.16 ~ 0.24) lg cfu	2.11 mg/L (1.63 ~ 2.73) 32.93 × MIC (25.39 ~ 42.70)	0.52 mg/L (8.32 × MIC)	0.9828

^acfu decrease (in lg units) at 24 h from the corresponding original cellular conidia, as extrapolated for infinitely high concentrations of voriconazole (note that a larger maximal relative activity corresponds to a more negative value of E_max)
^bcfu increase (in lg units) at 24 h from the corresponding original cellular conidia, as extrapolated for infinitely low concentrations of voriconazole
^cExposure (in extracellular concentration and multiple of corresponding MIC) causing a reduction halfway between the E_min and E_max values, as obtained from the hill equation by using a slope factor of − 1
^dExposure (in extracellular concentration and multiple of corresponding MIC) resulting in no apparent pathogen growth (the number of cfu was identical to that of the original cellular conidia), as determined by graphical interpolation
^eR is coefficient of correlation

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