Table 2.
Parameters# | 250 mg (n=12) | 500 mg (n=11) | ||||||
---|---|---|---|---|---|---|---|---|
Parent compounds | Metabolites | Parent compounds | Metabolites | |||||
MDS | ASS | MDA | ASA | MDS | ASS | MDA | ASA | |
Single dose oral administration, Day 1 (T0-24 h) | ||||||||
Cmaxa (µg/L) | 9.57 ± 3.34 | 5.18 ± 3.43 | 66.09 ± 17.09 | 79.76 ± 19.28 | 12.73 ± 2.73* | 9.81 ± 3.53* | 72.26 ± 16.33 | 102.32 ± 20.76 |
Tmaxb (h) | 1 [0.5] | 1.25 [0.625] | 1.5 [0.5] | 1.5 [0] | 1 [0.5] | 1 [3.5] | 1.5 [0.25] | 1.5 [0.5] |
AUCa (µg.h/L) | 75.38 ± 26.60 | 25.20 ± 29.15 | 410.35 ± 100.24 | 647.73 ± 117.41 | 141.16 ± 41.15* | 176.59 ± 177.06* | 476.02 ± 116.59 | 733.09 ± 149.90 |
Multiple dose oral administration, Day 7 (T0-72 h) | ||||||||
Parameters | MDS | ASS | MDA | ASA | MDS | ASS | MDA | ASA |
Cmaxa (µg/L) | 15.34 ± 6.96 | 10.93 ± 4.60 | 61.38 ± 20.47 | 78.23 ± 26.42 | 23.00 ± 4.99 | 12.77 ± 2.87 | 99.78 ± 27.57* | 170.35 ± 53.79* |
Tmaxb (h) | 1 [0.125] | 1 [0.125] | 2 [0.625] | 1.5 [0.5] | 1 [0.5] | 1 [0.5] | 1.5 [0.75] | 1.5 [0] |
AUCa (µg.h/L) | 162.27 ± 140.81 | 114.98 ± 54.12 | 437.49 ± 174.96 | 1013.55 ± 221.14 | 176.24 ± 72.68 | 106.82 ± 34.59 | 516.43 ± 156.64 | 1386.50 ± 332.86* |
Vd/Fa (L/kg) | 371.84 ± 386.32 | 155.55 ± 489.17 | 37.12 ± 28.53 | 10.53 ± 12.55 | 453.64 ± 376.55 | 458.14 ± 462.33 | 57.89 ± 24.35 | 23.39 ± 23.03 |
Cl/Fa (L/h/kg) | 27.99 ± 23.88 | 17.09 ± 13.52 | 3.29 ± 1.70 | 0.74 ± 0.25 | 31.33 ± 16.15 | 30.48 ± 15.50 | 5.09 ± 1.64 | 1.11 ± 0.49 |
t1/2a (h) | 8.06 ± 5.62 | 10.37 ± 8.84 | 8.25 ± 5.85 | 9.86 ± 9.77 | 9.97 ± 9.39 | 9.35 ± 8.18 | 8.71 ± 5.46 | 14.13 ± 12.79 |
Cmax maximum plasma concentration, Tmax time to reach maximum concentration, AUC area under the plasma concentration–time curve from time zero to the last measurable concentration, Vd/F the apparent volume of distribution, Cl/F the apparent clearance, t1/2 elimination half-life.
aData are expressed as mean ± SD; bdata is expressed as median [IQR]; * p < 0.05 for significant differences.
#The desired pharmacokinetic parameters of Vd, Cl and t1/2 of both the parent compounds during single oral administration (day 1, 24 h) were not included in this table. These parameters are omitted for the parent compounds because the slope in their elimination phase did not end at 24 h post-dosing. Therefore, these parameters were calculated only for the metabolites.