TABLE 2.
Population mean estimated pharmacokinetic parameters, median (25th to 75th percentiles) post hoc individual values, and derived parameters for each groupa
| Parameter | Group 1 (n = 30)
|
Group 2 (n = 37)
|
Group 3 (n = 33)
|
Pb | |||
|---|---|---|---|---|---|---|---|
| Population mean value (CV %) | Median post hoc individual value (IQR) | Population mean value (CV %) | Median post hoc individual value (IQR) | Population mean value (CV %) | Median post hoc individual value (IQR) | ||
| Experimental parameters | |||||||
| CL/F (ml · h−1) | 6,820 (196.6) | 3,691 (1,620-6,685) | 1,643 (181.7) | 1,718 (831-3,333) | 769 (151.3) | 851 (472-1,755) | <0.0001* |
| V/F (liter) | 837 (76.8) | 800 (771-832) | 534 (172.0) | 506 (483-570) | 403 (96.0) | 394 (361-402) | <0.0001* |
| ka (h−1) | 0.658 (28.5) | 0.622 (0.595-0.680) | 0.510 (56.0) | 0.507 (0.452-0.575) | 0.309 (60.8) | 0.307 (0.253-0.343) | <0.0001* |
| Tlag (h) | 1.94 (7.4) | 1.95 (1.86-2.00) | 1.41 (4.5) | 1.41 (1.41-1.41) | 0.97 (1.5) | 0.98 (0.95-0.99) | <0.0001* |
| SDREc (ng · ml−1) | 5.2 | 18.9 | 34.5 | ||||
| Derived parameters | |||||||
| kel (h−1)d | 8.15 | 5.62 (1.69-9.42) | 3.08 | 0.58 (0.18-1.29) | 1.91 | 2.35 (1.30-4.48) | <0.0001* |
| Cmax (ng · ml−1)e | 83 | 85 (43-128) | 131 | 116 (75-183) | 170 | 148 (85-226) | 0.0041A |
| Tmax (h)e | 2.5 | 2.45 (2.21-3.20) | 2.1 | 1.90 (1.90-2.40) | 2.1 | 1.90 (1.66-2.37) | 0.0335B |
| AUCd (ng · h · ml−1) | 88 | 165 (90-370) | 365 | 349 (179-767) | 780 | 705 (342-1,271) | <0.0001* |
a
CV %, percent coefficient of variation as calculated by P-PHARM; IQR, interquartile range (25th to 75th percentiles are given in parentheses).
b
*, all pairwise comparisons were significant. Superscripts: A, group 1 versus group 3; B, group 1 versus group 3. P values were estimated from the logarithm of the post hoc individual values.
c
SDRE, standard deviation of residual error.
d
Derived parameters calculated from CL/F, V/F, and dose.
e
Observed values on curves.