Pharmacokinetic parameters of voriconazole in mouse, rat, rabbit, guinea pig and dog following single and multiple administration by oral and intravenous routes
Parameter | Mouse | Rat | Rabbit | Guinea Pg | Dog | ||
|---|---|---|---|---|---|---|---|
| Sex | Male | Male | Female | Female | Femalea | Male/Female | |
| Number of animalsb | 3 | 2 | 2 | 3 | 1c | 4 | |
| Plasma protein binding (%) | 67 | 66 | 66 | 60 | 45 | 51 | |
| Intravenous | |||||||
| Dose (mg/kg) | 10 | 10 | 10 | 3 | 10 | 3 | |
| Single dose AUCt (μg · h/ml) | 41.7 | 18.6 | 81.6 | 1.1 | 38.5 | 32.1 | |
| Multiple dose AUCt (μg · h/ml)d | 8.0 | 6.7 | 13.9 | 1.6 | 22.0 | 17.9 | |
| Oral | |||||||
| Dose (mg/kg) | 30 | 30 | 30 | 10 | 10 | 6 | |
| Single-dose Cmax (μg/ml) | 12.4 | 9.5 | 16.7 | 1.0 | 4.1 | 6.5 | |
| Single-dose Tmax (h) | 2 | 6 | 1 | 1 | 8 | 3 | |
| Single-dose AUCt (μg · h/ml) | 98.8 | 90.0 | 215.6 | 3.2 | 29.0 | 88.8 | |
| Multiple-dose AUCt (μg · h/ml)d | 35.3 | 32.3 | 57.4 | 4.4 | 32.3 | 52.2 | |
| Apparent bioavailability (%) | 81 | 159 | 88 | 87 | 75 | 138 | |
↵ a Male animals were used for single oral dose study
↵ b Number of animals per time point, except for dog and rabbit studies, which involved serial bleeding
↵ c n = 3 per time point for single oral dose study in guinea pigs
↵ d Once daily for up to 10 days (minimum 5 days), except guinea pig multiple oral (three times daily)