TABLE 2.
CYP3A5*3*6*7 metabolic composite groups and associations to tacrolimus pharmacokinetics.
| Composite CYP3A5*3*6*7 Metabolic Groups |
Group Pairwise Comparison* |
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| Tacrolimus pharmacokinetic parameters | Poor (1) | Intermediate (2) | Extensive (3) | JT Trend P-value | 1 vs. 2 | 1 vs.3 | 2 vs. 3 |
| Mean/Std/N | Mean/Std/N | Mean/Std/N | |||||
| Study dose (mg) | 2.46/1.06/35 | 4.07/1.57/23 | 5.64/1.60/7 | <0.001 | <0.001 | <0.001 | 0.039 |
| Study dose/TBW (mg/kg) | 0.03/0.02/35 | 0.05/0.02/23 | 0.07/0.02/7 | <0.001 | 0.004 | 0.004 | 0.062 |
| C12h (ng/ml) | 6.99/1.83/35 | 7.70/1.88/23 | 6.77/1.67/7 | 0.550 | 0.737 | 0.808 | 0.808 |
| C12/dose (ng/ml/mg) | 3.32/1.64/35 | 2.13/0.81/23 | 1.31/0.63/7 | <0.001 | 0.005 | <0.001 | 0.011 |
| Cmax (ng/ml) | 16.89/6.90/35 | 20.41/8.14/23 | 20.81/13.48/7 | 0.129 | 0.249 | 1.000 | 1.000 |
| Cmax/Dose (ng/ml/mg) | 7.69/3.33/35 | 5.49/2.23/23 | 4.00/2.69/7 | <0.001 | 0.029 | 0.016 | 0.155 |
| T max (hr) | 1.81/0.81/35 | 2.17/1.50/23 | 1.52/0.54/7 | 0.954 | 0.729 | 0.729 | 0.580 |
| AUC 0–12 (ng.hr/ml) | 119.66/28.73/35 | 135.75/35.14/23 | 125.66/31.30/7 | 0.261 | 0.515 | 1.000 | 1.000 |
| AUC* (ng.hr/ml/mg) | 56.03/24.69/35 | 37.06/12.83/23 | 24.26/10.80/7 | <0.001 | 0.005 | 0.002 | 0.019 |
| CL_F (L/hr) | 21.14/8.02/35 | 30.79/12.19/23 | 47.43/17.30/7 | <0.001 | 0.008 | 0.002 | 0.019 |
| CL/LBW (L/hr/kg) | 0.38/0.16/35 | 0.55/0.27/23 | 0.91/0.40/7 | <0.001 | 0.036 | 0.003 | 0.044 |
| AUC 0–4 (ng.hr/ml/mg) | 51.20/15.22/35 | 60.77/20.07/23 | 56.89/19.24/7 | 0.153 | 0.285 | 1.000 | 1.000 |
| AUC∗ 0–4 hr (ng.hr/ml/mg) | 23.77/10.53/35 | 16.46/6.22/23 | 11.02/5.24/7 | <0.001 | 0.016 | 0.004 | 0.056 |
P-values from two-sided Jonckheere–Terpstra Trend (JT) test. *Post hoc pairwise comparisons using Holm-Bonferroni adjusted Wilcoxon rank sum tests.