TABLE 4.
Tacrolimus pharmacokinetics stratified by CYP3A5*3*6*7 metabolic composite groups and ABCB1 3435 genotypes.
|
ABCB1 3534 CC |
ABCB1 3534 CT and TT |
Significance |
||||||
| CYP3A5 Poor | CYP3A5 Intermediate | CYP3A5 Extensive | CYP3A5 Poor | CYP3A5 Intermediate | CYP3A5 Extensive | ABCB1 3435 | CYP3A5 Composite | |
| N | 13 | 10 | 6 | 20 | 10 | 6 | ||
| Study dose (mg) | 2.46 (0.36) | 4.00 (0.41) | 5.67 (0.53) | 2.35 (0.29) | 3.55 (0.41) | 5.08 (0.53) | 0.281 | 2.2E-08 |
| Study Dose/TBW (mg/kg) | 0.03 (0.01) | 0.05 (0.01) | 0.07 (0.01) | 0.03 (0.00) | 0.04 (0.01) | 0.06 (0.01) | 0.846 | 1.3E-05 |
| C12hr (ng/ml) | 6.94 (0.50) | 7.55 (0.58) | 7.40 (0.74) | 6.81 (0.41) | 8.37 (0.58) | 6.58 (0.74) | 0.930 | 0.107 |
| C12hr/dose (ng/ml/mg) | 3.44 (0.37) | 2.16 (0.43) | 1.43 (0.55) | 3.30 (0.30) | 2.40 (0.43) | 1.57 (0.55) | 0.814 | 2.3E-04 |
| Cmax (ng/ml) | 15.68 (2.23) | 18.62 (2.54) | 16.97 (3.29) | 16.96 (1.80) | 23.33 (2.54) | 23.67 (3.29) | 0.057 | 0.099 |
| Cmax/Dose (ng/ml) | 7.20 (0.81) | 5.21 (0.92) | 3.36 (1.19) | 8.09 (0.65) | 6.61 (0.92) | 4.95 (1.19) | 0.105 | 0.002 |
| Tmax (hr) | 1.94 (0.31) | 1.87 (0.35) | 1.78 (0.46) | 1.72 (0.25) | 2.29 (0.35) | 2.03 (0.46) | 0.628 | 0.740 |
| AUC* (ng.hr/ml) | 116.68 (8.54) | 130.75 (9.73) | 121.82 (12.57) | 117.75 (6.88) | 150.30 (9.73) | 129.45 (12.57) | 0.263 | 0.036 |
| AUC0–12 Dose (ng.hr/ml/mg) | 56.39 (5.64) | 36.76 (6.43) | 23.95 (8.30) | 56.80 (4.55) | 42.94 (6.43) | 28.97 (8.30) | 0.485 | 1.1E-04 |
| CL_F (L/hr) | 22.61 (2.94) | 31.30 (3.35) | 48.23 (4.32) | 20.09 (2.37) | 24.49 (3.35) | 39.53 (4.32) | 0.040 | 2.8E-07 |
| CL/LBW (L/hr/kg) | 0.37 (0.06) | 0.55 (0.07) | 0.90 (0.09) | 0.39 (0.05) | 0.41 (0.07) | 0.79 (0.09) | 0.218 | 7.2E-07 |
| AUC 0–4 h (ng.hr/mL/mg) | 48.59 (4.75) | 57.57 (5.41) | 51.85 (6.99) | 50.96 (3.83) | 68.17 (5.41) | 61.47 (6.99) | 0.110 | 0.032 |
Univariate results from multivariate analysis of variance. Values are Mean (Std).