TABLE 2.
Pharmacokinetic parameters of itraconazole and 7-hydroxyitraconazole after an oral administration of itraconazole at doses of 10, 30, and 50 mg/kg to ratsa
| Parameter | Value at dose (mg/kg) of:
|
||
|---|---|---|---|
| 10 (n = 8) | 30 (n = 10) | 50 (n = 10) | |
| Body wt (g) | 264 ± 13.7 | 274 ± 7.47 | 264 ± 4.12 |
| Itraconazole | |||
| AUC0-∞b (μg · min/ml) | 380 ± 76.3 | 2,060 ± 651 | 4,670 ± 969d |
| Terminal t1/2 (min) | 639 ± 182 | 864 ± 223 | 1,490 ± 616c |
| Cmaxb (μg/ml) | 0.658 ± 0.224e | 1.25 ± 0.450 | 2.34 ± 0.570 |
| Tmax (min) | 158 ± 201 | 273 ± 429 | 324 ± 532 |
| CLR (ml/min/kg) | BDf | 0.00850 ± 0.00168 | 0.0128 ± 0.0334 |
| Ae0-48 h (% of dose) | BD | 0.0543 ± 0.0152 | 0.270 ± 0.256 |
| GI48 h (% of dose) | 1.30 ± 0.686 | 1.55 ± 1.43 | 5.91 ± 4.34c |
| F (%) | 34.9 | 63.0 | 85.7 |
| 7-Hydroxyitraconazole | |||
| Cmaxb (μg/ml) | 0.615 ± 0.0963 | 1.51 ± 0.335 | 1.56 ± 0.306d |
| Tmax (min) | 345 ± 268e | 960 ± 617 | 1,060 ± 735 |
| AUC0-48 hb (μg · min/ml) | 1,000 ± 171 | 3,280 ± 572 | 3,690 ± 764c |
| Ae0-48 h (% of dose) | BD | 0.0405 ± 0.0142 | 0.124 ± 0.0890 |
| GI48 h (% of dose) | 0.773 ± 0.170 | 0.728 ± 0.246 | 0.848 ± 0.399 |
a
See Table 1, footnote a.
b
AUC0-∞, Cmax, and AUC0-48 h values were normalized to 10 mg/kg of itraconazole for statistical analysis.
c
The 50-mg/kg value was significantly different (P < 0.05) from those at 10 and 30 mg/kg.
d
Each group value was significantly different (P < 0.05).
e
The 10-mg/kg value was significantly different (P < 0.05) from those at 30 and 50 mg/kg.
f
BD, below detection limit.