Table 2.
Pharmacokinetic parameter values for each genotype group calculated with population pharmacokinetic predictions of 5th−5%, 5th−50%, 5th−95%, 50th−5%, 50th−50%, 50th−95%, 95th−5%, 95th−50%, and 95th−95% (percentage of total population−percentage in range), as a result of the fexofenadine population pharmacokinetic model visual predictive check established by considering the organic-anion-transporting-polypeptide 1B1 (OATP1B1) genetic polymorphism as a covariate [following multiple oral exposures to 180 mg fexofenadine (12 h interval and 10 times dosing)]. The 5th, 50th, and 95th mean 5th, 50th, and 95th percentiles of the predicted concentrations for each group; the 5%, 50%, and 95% mean 5%, 50%, and 95% confidence interval (CI) ranges in each percentile.
| Parameters |
SLCO1B1 521T > C genotypes |
||
|---|---|---|---|
| TT | TC | CC | |
| t1/2 (h) | 1.97 ± 0.63 | 1.84 ± 0.25 | 2.09 ± 0.46 |
| tmax (h) | 1.84 ± 0.29 | 1.93 ± 0.15 | 2.39 ± 0.31∗ |
| cmax (ng/mL) | 470.17 ± 137.78∗ | 593.83 ± 175.80∗ | 846.32 ± 268.89∗ |
| AUC108−120 (h·ng/mL) | 2633.14 ± 917.84∗ | 3518.62 ± 1227.54∗ | 5793.46 ± 2100.82∗ |
| AUC108−∞ (h·ng/mL) | 2750.95 ± 1013.51∗ | 3671.18 ± 1324.20∗ | 6231.77 ± 2445.98∗ |
| V/F (L) | 191.14 ± 36.08∗ | 145.23 ± 62.91∗ | 92.15 ± 14.61∗ |
| CL/F (L/h) | 73.41 ± 26.55∗ | 54.89 ± 19.87∗ | 32.98 ± 12.94∗ |
| MRT (h) | 4.35 ± 0.34∗ | 4.54 ± 0.23∗ | 5.27 ± 0.42∗ |
| cSS,mean (ng/mL) a | 219.49 ± 76.53∗ | 293.26 ± 102.35∗ | 482.70 ± 175.10∗ |
| AUC ratio b | 1.04 ± 0.02 | 1.04 ± 0.01 | 1.07 ± 0.03∗ |
cSS,mean was the mean plasma concentration of fexofenadine at steady-state.
The AUC ratio was the ratio for single and multiple exposures to fexofenadine and was calculated by the following formula: AUC108−∞ (according to multiple exposures)/AUC0−∞ (according to single exposure).
∗P < 0.05 between SLCO1B1 521TT, TC, and CC groups. T: thymine; C: cytosine; t1/2: half-life; cmax: peak plasma concentration; tmax: time to reach cmax; AUC: area under the time-plasma concentration curve; V/F: volume of distribution; CL/F: clearance; MRT: mean residence time.