Table 3.
Pharmacokinetic parameters (normalized by the mean of each drug) according to CYP3A genotypes and phenotype and sex in all the included drugs.
| Gene | Genotype/Phenotype | Pharmacokinetic Parameter | |||||
|---|---|---|---|---|---|---|---|
| Normalized AUC | Normalized Cmax | Normalized T1/2 | Normalized Tmax | Normalized Cl | Normalized Vd | ||
| CYP3A4 | *1/*1 (n = 233) | 0.99 (0.35) | 0.99 (0.42) | 0.99 (0.32) | 1.00 (0.56) | 0.99 (0.38) | 1.00 (0.37) |
| *1/*20 (n = 5) | 1.12 (0.24) | 0.96 (0.33) | 1.18 (0.24) | 0.66 (0.27) | 0.73 (0.18) | 0.90 (0.10) | |
| *1/*22 (n = 11) | 1.06 (0.46) | 0.98 (0.38) | 0.99 (0.18) | 1.00 (0.71) | 0.96 (0.43) | 0.98 (0.43) | |
| *1/*3 + *3/*22 (n = 2) | 1.24 (0.40) | 1.25 (0.10) | 1.07 (0.28) | 0.93 (0.03) | 0.75 (0.39) | 0.83 (0.18) | |
| p-value | 0.523 | 0.738 | 0.566 | 0.482 | 0.338 | 0.874 | |
| CYP3A4 | Wild-type (n = 233) | 0.99 (0.35) | 0.99 (0.42) | 0.99 (0.32) | 1.00 (0.56) | 0.99 (0.37) | 1.00 (0.37) |
| Mutated (n = 18) | 1.10 (0.39) | 1.00 (0.34) | 1.05 (0.20) | 0.90 (0.58) | 0.87 (0.37) | 0.94 (0.34) | |
| p-value | 0.240 | 0.853 | 0.276 | 0.351 | 0.146 | 0.428 | |
| CYP3A5 | *1/*1 (n = 5) | 0.90 (0.30) | 1.13 (0.48) | 0.88 (0.19) | 0.73 (0.26) | 1.20 (0.51) | 1.05 (0.27) |
| *1/*3 (n = 45) | 1.02 (0.32) | 1.02 (0.44) | 1.04 (0.36) | 0.90 (0.52) | 0.94 (0.38) | 0.96 (0.23) | |
| *3/*3 + *3/*6 + *3/*7 (n = 201) | 0.99 (0.37) | 0.99 (0.40) | 0.99 (0.31) | 1.03 (0.57) | 0.98 (0.38) | 1.00 (0.39) | |
| p-value | 0.710 | 0.626 | 0.731 | 0.257 | 0.486 | 0.833 | |
| CYP3A | EM (n = 50) | 1.01 (0.31) | 1.03 (0.44) | 1.02 (0.35) | 0.88 (0.50) | 0.97 (0.39) | 0.97 (0.23) |
| IM (n = 183) | 0.99 (0.37) | 0.99 (0.41) | 0.98 (0.31) | 1.03 (0.57) | 0.99 (0.37) | 1.01 (0.40) | |
| PM (n = 18) | 1.09 (0.39) | 1.00 (0.34) | 1.05 (0.21) | 0.93 (0.59) | 0.87 (0.37) | 0.94 (0.34) | |
| p-value | 0.408 | 0.692 | 0.501 | 0.155 | 0.324 | 0.720 | |
| Sex | Men (n = 149) | 1.00 (0.37) | 1.00 (0.43) | 0.96 (0.30) | 0.99 (0.58) | 0.99 (0.38) | 0.96 (0.32) |
| Women (n = 102) | 0.99 (0.35) | 1.00 (0.39) | 1.05 (0.34) | 1.01 (0.54) | 0.97 (0.37) | 1.06 (0.41) | |
| p-value | 0.765 | 0.832 | 0.030 | 0.426 | 0.889 | 0.057 | |
Abbreviation: AUC, area under the curve; Cmax, maximum plasma concentration; Tmax, time to reach the maximum plasma concentration; T1/2, half-life; Cl, total drug clearance adjusted for bioavailability; Vd, volume of distribution adjusted for bioavailability; CYP, cytochrome p450 oxidase.