Table 1.
Predicted oral/intravenous (PO/IV) doses and steady-state/trough concentrations (Css/Cmin) ratios after IV tacrolimus infusion and PO administration for similar simulated AUCτ in different clinical scenarios.
| Administration Route PO | Administration Route IV | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Dose PO (mg/12 H) | AUCτ (ng/mL·h) (Geometric Mean) | Cmin (ng/mL) | Dose IV (mg/24 H) | AUCτ (ng/mL·h) (Geometric Mean) | Css (ng/mL) | Ratio AUCτ | Ratio PO/IV Dose | Ratio Css/Cmin | |
| Healthy volunteers | 1 | 95.29 [90%CI 81.84–110.95] | 5.77 [90%CI 4.86–6.84] | 0.47 | 95.91 [90%CI 87.59–105.02] | 8.06 [90%CI 7.36–8.83] | 1.00 | 4.25 | 1.40 |
| Clinical case (virtual twin) | 1 | 103.67 [90%CI 86.19–124.70] | 7.09 [90%CI 5.83–8.62] | 0.51 | 104.84 [90%CI 85.43–128.65] | 8.85 [90%CI 6.82–10.21] | 0.99 | 3.92 | 1.25 |
| Both donor and recipient expressing CYP3A5 (*1/*1) | 1 | 30.76 [90%CI 28.11–33.65] | 1.50 [95%CI 1.34–1.67] | 0.30 | 30.27 [90%CI 28.31–32.37] | 2.53 [90%CI 2.36–2.70] | 1.00 | 6.67 | 1.69 |
| Donor expressing CYP3A5 (*1/*1) | 1 | 50.52 [90%CI 45.41–56.21] | 2.44 [90%CI 2.16–2.76] | 0.50 | 50.80 [90%CI 47.16–54.73] | 4.24 [90%CI 3.94–4.57] | 0.99 | 4.0 | 1.74 |
| Recipient expressing CYP3A5 (*1/*1) | 1 | 78.55 [90%CI 71.71–86.03] | 5.05 [90%CI 4.58–5.57] | 0.32 | 79.78 [90%CI 74.45–85.49] | 6.72 [90%CI 3.94–4.57] | 0.98 | 6.25 | 1.33 |
| CYP3A inhibitor (itraconazole PO) healthy volunteers | 1 | 333.11 [90%CI 258.88–388.14] | 22.62 [90%CI 19.16–26.71] | 1.15 | 335.60 [90%CI 301.76–373.22] | 29.03 [90%CI 26.11–32.27] | 0.99 | 1.74 | 1.28 |
| CYP3A inhibitor (itraconazole IV) healthy volunteers | 1 | 158.85 [90%CI 134.31–187.88] | 10.36 [90%CI 8.62–12.46] | 0.50 | 159.62 [90%CI 143.20–178.58] | 13.94 [90%CI 12.49–15.56] | 1.00 | 4.00 | 1.35 |