Table 3.
Amount of voriconazole and its metabolites excreted in urine over 96 h after oral and intravenous administration of a single 400 mg (= 1.145 mmol) dose of voriconazole to 20 healthy participants; the data are sorted according to the CYP2C19 genotypes
| Before hydrolysis | After hydrolysis | |||||||
|---|---|---|---|---|---|---|---|---|
| i.v. (µmol) | Oral (µmol) | i.v. (µmol) | Oral (µmol) | |||||
| Mean | SD | Mean | SD | Mean | SD | Mean | SD | |
| EM (n= 8) | ||||||||
| Voriconazole | 6.7 | 3.8 | 4.4 | 2.6 | 9.8 | 3.8 | 6.8 | 3.7 |
| Voriconazole-N-oxide | 14.7 | 8.8 | 17.3 | 8.1 | 24.1 | 7.5 | 23.1 | 7.9 |
| OH-voriconazole | 29.1 | 10.4 | 34.3 | 10.6 | 38.9 | 19.2 | 40.9 | 12.9 |
| DiOH-voriconazole | 132 | 53.1 | 128 | 43.7 | 144 | 51.6 | 133 | 50.1 |
| HEM (n= 8) | ||||||||
| Voriconazole | 10.7 | 3.7 | 6.5 | 2.3 | 16.8a | 4.5 | 12.1 | 5.6 |
| Voriconazole-N-oxide | 20.5 | 6.8 | 27.1 | 10.8 | 26.3 | 10.2 | 25.8 | 8.7 |
| OH-voriconazole | 43.8 | 16.3 | 45.0 | 19.1 | 63.8a | 19.1 | 61.0a | 17.0 |
| DiOH-voriconazole | 134 | 43.5 | 142 | 39.5 | 148 | 65.6 | 156 | 52.9 |
| PM (n= 4) | ||||||||
| Voriconazole | 10.7 | 2.3 | 9.0b | 2.7 | 18.2b | 2.8 | 17.6b | 4.3 |
| Voriconazole-N-oxide | 20.6 | 6.0 | 22.1 | 3.2 | 27.6 | 8.9 | 31.0 | 11.8 |
| OH-voriconazole | 50.5b | 13.8 | 60.2b | 19.5 | 38.9 | 9.6 | 42.7 | 9.9 |
| DiOH-voriconazole | 158 | 47.1 | 165 | 54.5 | 158 | 56.2 | 172 | 61.3 |
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.