Table 2.
Parameters of the pharmacokinetic models developed using ITSIM and Pmetrics for tacrolimus (TAC) once daily (OD) and TD (twice daily) on day 7 (D7) and week 6 (W6)
| TAC OD D7 | TAC OD W6 | |||||||
|---|---|---|---|---|---|---|---|---|
| ITSIM | Pmetrics | ITSIM | Pmetrics | |||||
| Median | Range | Median | Range | Median | Range | Median | Range | |
| C 0 (μg/mL) | 0.57 | 0.1–1.23 | 0.57 | 0.06–1.21 | 0.73 | 0.29–2.32 | 0.73 | 0.29–2.39 |
| a1 | 4.88 | 1.59–9.89 | 7.26 | 0.06–11.94 | 6.00 | 1.00–12.05 | 7.00 | 0.56–12.94 |
| b1 (/h) | 6.33 | 1.36–12.48 | 13.8 | 0.23–14.93 | 6.82 | 1.52–14.48 | 9.49 | 0.57–14.93 |
| a2 | 15.57 | 2.98–31.52 | 9.52 | 0.27–34.83 | 10.82 | 3.90–35.32 | 10.80 | 1.18–35.83 |
| b2 (/h) | 2.36 | 0.37–5.18 | 5.19 | 0.09–5.97 | 1.78 | 0.28–4.63 | 1.83 | 0.04–4.98 |
| R | 0.71 | 0.39–1.00 | 0.58 | 0.02–0.91 | 0.66 | 0.01–1.00 | 0.53 | 0.01–0.87 |
|
FAIV
(ng/mL) |
1.93 | 1.00–5.65 | 1.70 | 0.35–2.99 | 2.43 | 1.11–6.00 | 3.18 | 0.99–5.97 |
| α (/h) | 0.26 | 0.07–1.40 | 0.20 | 0.08–0.83 | 0.25 | 0.13–0.43 | 0.27 | 0.10–0.76 |
| Vd/F (L) | 515 | 177.0–1000.0 | 589 | 335–2857 | 412 | 167–901 | 314 | 167–1010 |
| Cl/F (L/h) | 48.5 | 19.2–91.7 | 48.7 | 18.9–91.3 | 35.1 | 15.8–80.1 | 35.3 | 15.7–81.5 |
| C 0 (μg/mL) | 1.27 | 0.53–3.53 | 1.30 | 0.62–3.46 | 1.66 | 0.83–8.52 | 1.60 | 0.75–8.65 |
| a1 | 10.26 | 3.08–15.74 | 11.90 | 0.09–16.92 | 12.64 | 6.03–18.33 | 10.68 | 1.89–18.91 |
| b1 (/h) | 17.00 | 7.17–24.64 | 12.25 | 0.88–24.88 | 17.93 | 12.18–23.19 | 13.38 | 1.38–24.88 |
| a2 | 11.83 | 7.95–14.28 | 13.1 | 5.05–14.95 | 10.25 | 5.04–15.23 | 8.17 | 1.73–14.93 |
| b2 (/h) | 9.25 | 2.56–20.77 | 12.81 | 3.09–20.91 | 7.24 | 1.89–10.07 | 5.90 | 0.35–9.95 |
| R | 0.58 | 0.01–1.00 | 0.55 | 0.07–1.00 | 0.74 | 0.06–1.00 | 0.56 | 0.06–1.00 |
|
FAIV
(ng/mL) |
3.12 | 1.27–9.96 | 3.60 | 2.25–9.95 | 4.98 | 0.97–9.53 | 6.30 | 1.75–9.95 |
| α (/h) | 0.39 | 0.10–0.68 | 0.44 | 0.21–1.00 | 0.44 | 0.25–0.77 | 0.55 | 0.26–1.00 |
| Vd/F (L) | 321 | 100–787 | 278 | 101–444 | 214 | 105–1030 | 159 | 100–571 |
| Cl/F (L/h) | 40.1 | 20.1–75.9 | 39.3 | 20.1–75.6 | 34.1 | 9.0–78.7 | 35.1 | 9.0–73.0 |
a1, b1, a2 and b2, shape and scale of the 2 γ‐distributions; r, the fraction of dose absorbed following the first γ‐distribution; C0, the model estimated trough level for a theoretical dose of 1000 mg, FAIV, the absolute bioavailability factor with respect to the IV route multiplied by the maximum concentration which would have been reached after a theoretical bolus IV of the reference dose; α, the elimination parameter; D7, day 7; OD, Advagraf; TAC, tacrolimus; TD, Prograf; W6, week 6; Vd/F, apparent volume of distribution calculated as theoretical dose/FAIV; Cl/F, apparent clearance calculated as dose/AUC.