Table 4.
Renal clearances of voriconazole and its metabolites and partial metabolic clearances of voriconazole (N-oxide and hydroxylation) after oral and intravenous administration of a single 400 mg dose of voriconazole to 20 healthy participants; the data are sorted according to the CYP2C19 genotypes
| CLR (ml min−1) | CLR (ml min−1) | CLR (ml min−1) | CLR (ml min−1) | |||||
|---|---|---|---|---|---|---|---|---|
| i.v. | Oral | i.v. | Oral | |||||
| Mean | SD | Mean | SD | Mean | SD | Mean | SD | |
| EM (n= 8) | ||||||||
| Voriconazole | 2.3 | 1.3 | 1.9 | 0.8 | ||||
| Voriconazole-N-oxide | 6.4 | 5.0 | 5.5 | 2.4 | 9.0 | 5.2 | 11.4 | 6.1 |
| OH-voriconazole | 145 | 54.5 | 186 | 75.3 | 72.8 | 52.5 | 99.0 | 96.7 |
| DiOH-voriconazole | 392 | 133 | 376 | 183 | ||||
| HEM (n = 8) | ||||||||
| Voriconazole | 1.8 | 0.6 | 1.4 | 0.7 | ||||
| Voriconazole-N-oxide | 11.4 | 8.3 | 12.6a | 8.8 | 4.3a | 1.4 | 5.3a | 2.2 |
| OH-voriconazole | 265a | 96.7 | 270 | 126 | 36.0 | 15.1 | 47.9 | 23.8 |
| DiOH-voriconazole | 462 | 165 | 480 | 160 | ||||
| PM (n = 4) | ||||||||
| Voriconazole | 1.4 | 0.4 | 1.3 | 0.4 | ||||
| Voriconazole-N-oxide | 11.4 | 5.5 | 10.9 | 5.1 | 3.7 | 1.5 | 4.5 | 2.1 |
| OH-voriconazole | 372b | 264 | 306 | 70.7 | 26.1 | 8.4 | 29.6b | 7.0 |
| DiOH-voriconazole | 435 | 106 | 493 | 123 | ||||
a
*1/*1 vs.*1/*2 P < 0.05.
b
*1/*1 vs.*2/*2 P < 0.05. EM, extensive metabolizers; HEM, heterozygous extensive metabolizer; PM, poor metabolizers.