Table 2. Tacrolimus pharmacokinetics parameters in whole blood and PBMC (n = 32).
Median [range] | Mean (SD) | |
---|---|---|
Dose (mg/12 h) | 1.5 [0.5–4] | 1.8 (1.0) |
Dose (mg/kg/12h) | 0.017 [0.005–0.048] | 0.021 (0.012) |
Whole blood pharmacokinetics (WB) | ||
Cmax (ng/mL) | 17.7 [3.5–36.3] | 16.4 (6.9) |
Cmax/dose (ng/mL/mg) | 9.5 [3.0–21.4] | 10.8 (5.2) |
Tmax (h) | 1.6 [0.2–6] | 1.9 (1.4) |
C0 (ng/mL)a | 6.2 [2.5–10.0] | 6.4 (2.2) |
C0/dose (ng/mL/mg) | 3.9[1.1–17.7] | 5.1 (4.2) |
AUC0–12h (ng∙h/mL) | 102.3 [35.0–215.5] | 108.9 (38.9) |
Cl/F (L.h-1) | 16.2 [5.0–39.2] | 17.8 (9.0) |
Intracellular pharmacokinetics (PBMC) | ||
Cmax (pg/million PBMC) | 71.3 [25.7–156.0] | 78.1 (37.1) |
Cmax/dose (pg/million PBMC/mg) | 44.2[17.1–258.7] | 56.1 (46.1) |
Tmax (h) | 1.6 [0.3–6] | 1.9 (1.2) |
C0 (pg/million PBMC) | 28.4 [9.6–80.4] | 37.2 (17.7) |
C0/dose (pg/million PBMC/mg) | 20.0 [3.2–67.2] | 24.8 (16.8) |
AUC0–12h (pg∙h/million PBMC) | 491.6 [223.0–1127.2] | |
Whole blood—intracellular relationships | ||
Intracellular diffusion ratio (AUC0–12h PBMC / AUC0–12h WB) |
23.6 [14.8–39.7] | 24.9 (6.9) |
r2 (p) | ||
Correlation AUC0–12h PBMC & AUC0–12h WB | 0.51 (<0.001) | |
Correlation C0PBMC & C0WB | 0.39 (<0.001) | |
Correlation CmaxPBMC & CmaxWB | 0.53 (<0.001) | |
Correlation CmaxPBMC & C0WB | 0.17 (0.02) | |
Correlation AUC0–12h PBMC & C0WB | 0.53 (<0.001) |
Cmax: maximum concentration; Tmax: time when Cmax is achieved; C0: predose concentration; AUC0-12h: area under the concentration–time curve from 0h to 12h; Cl/F: apparent clearance; PBMC: peripheral blood mononuclear cells; WB: whole blood; SD: standard deviation; r2: coefficient of determination; p: p-value
a: the day of the study, 81.2% of patients had tacrolimus whole blood concentration between 4–10 ng/mL.