Observed and predicted pharmacokinetics parameters across CYP2C19 genotypes following a single oral dose of 400 mg voriconazole
A two-compartment model with first-order absorption was found to adequately fit the biphasic plasma concentration-time profiles of CYP2C19*1/*1 observed in the Weiss et al., 2009 study by using Phoenix 64. In the model, the estimated rate of absorption parameter values (k01), rate of elimination from central compartment parameter values (k10), rate of transfer from central to peripheral compartment parameter values (k12), and rate of transfer from peripheral to central compartment (k21) were 0.90, 0.28, 0.29, and 0.14 h−1, respectively.
| CYP2C19 Genotype Group | N | k10a | Observed | Predicted | ||
|---|---|---|---|---|---|---|
| Cmax (µg/ml) | CLpo Mean (l/h) | Cmax (µg/ml) | CLpo Mean (l/h) | |||
| *1/*1 | 9 | 0.28 | 3.1 | 27.84 | 2.35 | 22.01 |
| *1/*2 | 11 | 0.17 | 2.84 | 19.05 | 2.57 | 13.4 |
| *2/*2 | 5 | 0.098 | 3.13 | 9.72 | 2.75 | 7.88 |
| *1/*17 | 8 | 0.43 | 2.16 | 31.53 | 2.1 | 33.88 |
↵a k10 in CYP2C19*1/*1 was a fitted value. The k10 in other CYP2C19 variants was calculated using eq. 4.