Table 4.
Pharmacokinetic parameters for midazolam, α-hydroxy-midazolam and voclosporin after oral administration of midazolam 7.5 mg alone and with voclosporin 0.4 mg kg−1 every 12 h
| Parameter | Midazolam | α-Hydroxy-midazolam | Voclosporin | ||
|---|---|---|---|---|---|
| Midazolam alone (n = 22) | Midazolam + voclosporin (n = 22) | Midazolam alone (n = 22) | Midazolam + voclosporin (n = 22) | Midazolam + voclosporin (n = 22) | |
| Tmax (h) | 0.5 (0.5–1) | 1 (0.25–1.5) | 0.5 (0.5–1.5) | 1 (0.5–2) | 2 (1–4) |
| Cmax (ng ml−1) | 43 469 ± 26 534 | 37 641 ± 18 014 | 16 121 ± 6500 | 13 661 ± 6983 | 134.6 ± 35.8 |
| GMR % (90% CI) | – | 88.86 | – | 81.93 | – |
| (79.92–98.79) | (69.32–96.85) | ||||
| AUC(0–24)* (h ng ml−1) | 124 038 ± 92 674 | 125 904 ± 90 724 | 38 690 ± 12 185 | 39 199 ± 10 230 | 569.3 ± 229.2 |
| GMR % (90% CI) | – | 101.72 | – | 102.73 | – |
| (92.83–111.47) | (93.79–112.51) | ||||
| AUC(inf) (h ng ml−1) | 127 682 ± 99 577 | 130 604 ± 99 542 | 40 518 ± 13 016 | 41 472 ± 11 561 | – |
| GMR % (90% CI) | – | 102.11 | – | 103.64 | – |
| (94.60–113.54) | |||||
| (93.41–111.63) | |||||
| t1/2 (h) | 4.8 ± 1.2 | 5.0 ± 1.3 | 6.9 ± 5.5 | 6.8 ± 5.4 | – |
Values are shown as means ± SD except Tmax, for which the median (range) is reported. Abbreviations are as follows: AUC, area under the curve; CI, confidence interval; Cmax, maximal concentration; GMR, geometric least squares mean ratio (comparison to midazolam alone) based on analysis of natural log-transformed data; Tmax, time to reach maximal concentration.
*
AUC(0–12) for voclosporin data.