Pharmacokinetic parameters of tacrolimus and its primary metabolites before and during CYP3A4 inhibition in 16 healthy volunteers (cohort B)
| Variable | Baseline | CYP3A4 Inhibition | Difference | P |
|---|---|---|---|---|
| % | ||||
| Tacrolimus | ||||
| AUC0–24 (h⋅ng/ml) | 50.6 ± 21.6 | 167.9 ± 73.2 | +232 | <0.001 |
| CL/F (l/h) | 69.7 ± 28.9 | 21.4 ± 9.3 | −69 | <0.001 |
| Midazolam | ||||
| CL/F (ml/min) | 762.7 ± 327.7 | 83.4 ± 24.9 | −89.1 | <0.001 |
| AUC1′-HOMDZ/AUCMDZ | 0.434 ± 0.133 | 0.041 ± 0.013 | −90.6 | <0.001 |
| AUC4-HOMDZ/AUCMDZ | 0.081 ± 0.017 | 0.030 ± 0.009 | −63.0 | <0.001 |
| Tacrolimus metabolites | ||||
| AUC13-DMT/AUCtacrolimus | 0.065 ± 0.028 | 0.107 ± 0.038 | +65 | <0.001 |
| AUC15-DMT/AUCtacrolimus | 0.025 ± 0.006 | 0.053 ± 0.014 | +112 | <0.001 |
| AUC31-DMT/AUCtacrolimus | 0.004 ± 0.002 | 0.005 ± 0.002 | +25 | 0.007 |
| AUCmetabolites/AUCtacrolimus | 0.094 ± 0.030 | 0.166 ± 0.040 | +77 | <0.001 |
AUCmetabolites, sum of AUC for 13-DMT, 15-DMT, and 31-DMT.