Table 2.
Tacrolimus dose, concentration, and area under the 12-h concentration curve.
| CYP3A5 expressers | CYP3A5 non-expressers | P value | |||
|---|---|---|---|---|---|
| Placebo (n = 12) | Diltiazem (n = 11) | Placebo (n = 8) | Diltiazem (n = 9) | ||
| 2 days before transplantation | |||||
| Daily dose, mg/day | 6.0 (6.0, 6.8) | 5.0 (5.0, 6.0) | 5.5 (5.0, 8.0) | 6.0 (5.0, 6.5) | 0.414a |
| Daily dose, mg/kg/day | 0.10 (0.08, 0.10) | 0.10 (0.09, 0.11) | 0.10 (0.09, 0.11) | 0.10 (0.09, 0.11) | 0.820a |
| Day 1 post-transplantation | |||||
| Daily dose, mg/day | 6.0 (6.0, 7.0) | 5.0 (5.0, 7.0) | 6.0 (5.0, 7.8) | 6.0 (4.5, 6.0) | 0.266a |
| Daily dose, mg/kg/day | 0.10 ± 0.02 | 0.11 ± 0.02 | 0.10 ± 0.03 | 0.09 ± 0.02 | 0.396b |
| Dose, mg/kg | 0.05 ± 0.01 | 0.06 ± 0.01 | 0.05 ± 0.02 | 0.05 ± 0.01 | 0.396b |
| C0, ng/mL | 7.0 ± 3.2 | 10.9 ± 3.7 | 12.6 ± 7.2 | 13.1 ± 7.4 | 0.055b |
| C0/D, ng/mL per mg | 2.2 (1.3, 2.8) | 3.3 (2.6, 4.5) | 3.8 (2.0, 5.0) | 3.8 (2.7, 7.2)c | 0.026a |
| C0/Daily dose, ng/mL per mg/day | 1.1 (0.6, 1.4) | 1.6 (1.3, 2.3) | 1.9 (1.0, 2.5) | 1.9 (1.3, 3.6)c | 0.026a |
| Day 3 post-transplantation | |||||
| Daily dose, mg/day | 7.5 ± 1.6 | 5.4 ± 1.7 | 5.1 ± 2.1 | 4.4 ± 2.4c | 0.005b |
| Daily dose, mg/kg/day | 0.12 ± 0.04 | 0.10 ± 0.04 | 0.09 ± 0.04 | 0.08 ± 0.05 | 0.092b |
| Dose, mg/kg | 0.06 ± 0.02 | 0.05 ± 0.02 | 0.04 ± 0.02 | 0.04 ± 0.03 | 0.092b |
| C0, ng/mL | 6.2 (4.4, 8.0) | 9.3 (7.0, 10.4) | 9.4 (8.8, 12.4)c | 11.9 (8.8, 13.4)c | < 0.001a |
| C0/D, ng/mL per mg | 1.8 (1.1, 2.0) | 3.7 (2.4, 4.5)c | 3.4 (2.7, 5.8)c | 6.4 (4.1, 8.8)c | < 0.001a |
| C0/Daily dose, ng/mL per mg/day | 0.9 (0.6, 1.0) | 1.8 (1.2, 2.2)c | 1.7 (1.4, 2.9)c | 3.2 (2.0, 4.4)c | < 0.001a |
| Day 7 post-transplantation | |||||
| Daily dose, mg/day | 8.8 (8.0, 11.8) | 6.0 (5.5, 8.0)c | 6.2 (5.0, 6.9)c | 3.5 (2.8, 6.2)c | < 0.001a |
| Daily dose, mg/kg/day | 0.17 ± 0.08 | 0.12 ± 0.04 | 0.10 ± 0.03 | 0.08 ± 0.04d | 0.004b |
| Dose, mg/kg | 0.08 ± 0.04 | 0.06 ± 0.02 | 0.05 ± 0.01 | 0.04 ± 0.02d | 0.004b |
| C0, ng/mL | 9.2 ± 1.6 | 7.4 ± 2.1 | 8.6 ± 2.5 | 8.4 ± 1.8 | 0.188b |
| C0/D, ng/mL per mg | 2.0 (1.4, 2.5) | 1.9 (1.8, 3.2) | 2.8 (2.5, 3.4) | 4.2 (2.8, 6.0)c | 0.009a |
| C0/Daily dose, ng/mL per mg/day | 1.0 (0.7, 1.2) | 1.0 (0.9, 1.6) | 1.4 (1.2, 1.7) | 2.1 (1.4, 3.0)c | 0.009a |
| AUC, ng*h/mL | 168.8 ± 32.2 | 138.1 ± 29.6 | 158.8 ± 40.7 | 147.8 ± 25.5 | 0.144b |
| AUC/D, ng*h/mL per mg | 34.9 (31.6, 38.5) | 43.6 (37.0, 50.5) | 49.4 (43.0, 62.9)c | 71.1 (54.9, 100.7)c | < 0.001a |
Values are expressed as mean ± SD or median (interquartile range) for comparison reasons.
AUC area under the concentration over 12-h curve, AUC/D dose-adjusted area under the concentration over 12-h curve, C0 trough concentration, C0/D dose-adjusted trough concentration.
aKruskal–Wallis test.
bAnalysis of variance.
cP < 0.05 versus CYP3A5 expressers with placebo group (Bonferroni correction for multiple comparisons).
dP < 0.05 versus CYP3A5 expressers with placebo group (Dunnett’s T3 correction for multiple comparisons).