Table 3.
Summary of pharmacokinetic parameters of two voriconazole formulations by CYP2C19 genotype
| Cmax (μg/L)
|
AUClast (hr⋅μg/L)
|
AUCinf (hr⋅μg/L)
|
|||||||
|---|---|---|---|---|---|---|---|---|---|
| SYP-1018 | Vfend® | Geometric mean ratio (90% CI)a | SYP-1018 | Vfend® | Geometric mean ratio (90% CI)a | SYP-1018 | Vfend® | Geometric mean ratio (90% CI)a | |
| EM (N=19) | 1,948.1±342.3 | 2,030.5±395.1 | 0.96 (0.87–1.05) | 5,671.7±1,258.2 | 5,893.3±1,075.1 | 0.95 (0.89–1.02) | 6,065.0±1,394.3 | 6,305.3±1,192.2 | 0.95 (0.87–1.04) |
| IM (N=19) | 2,101.2±488.0 | 2,218.0±572.4 | 0.94 (0.86–1.03) | 7,431.1±2,592.8 | 7,703.5±2,455.0 | 0.95 (0.89–1.03) | 8,314.1±3,374.3 | 8,433.0±3,033.9 | 0.97 (0.88–1.06) |
| PM (N=10) | 2,535.6±514.9 | 2,319.5±367.2 | 1.11 (0.97–1.26) | 12,950.7±2,908.8 | 13,742.6±2,384.4 | 0.94 (0.85–1.04) | 19,690.8±7,559.1 | 21,638.1±8,460.0 | 0.91 (0.80–1.03) |
| *1/*17 (N=1) | 2,077.0 | 1,866.0 | NA | 4,619.1 | 4,317.4 | NA | 4,917.4 | 4,591.4 | NA |
| *2/*17 (N=2) | 1,869.0 | 1,935.5 | NA | 9,444.5 | 8,015.3 | NA | 11,554.6 | 9,514.2 | NA |
Notes: Values are presented as mean ± standard deviation except for *1/*17 and *2/*17, which is presented as individual value (*1/*17) or mean (*2/*17);
a
SYP-1018 to Vfend®.
Abbreviations: Cmax, maximum plasma concentration; AUClast, area under the concentration–time curve (AUC) from dosing to the last quantifiable concentration; AUCinf, AUC from dosing to infinity; CI, confidence interval; EM, extensive metabolizer; IM, intermediate metabolizer; PM, poor metabolizer; NA, not applicable; hr, hours.