Table 1.
Effects of DAC HYP 150 mg SC every 4 weeks on the primary PK parameters of CYP probes: summary of analysis of variance
| Probe drug | Parameter (unit) | n | Mean (%CV) | Ratio ([probe drug + DAC HYP]/probe drug alone) | 90% CI for the ratio | |
|---|---|---|---|---|---|---|
| Probe drug alone | Probe drug + DAC HYP | |||||
| Midazolam | AUC(0–inf) (ng h ml−1) | 19 | 800.8 (41) | 816.9 (49) | 1.01 | 0.89–1.15 |
| Cmax (ng ml−1) | 19 | 278 (38) | 311 (48) | 1.01 | 0.90–1.26 | |
| t1/2 (h) | 19 | 5.68 (25) | 5.57 (25) | NC | NC | |
| S‐warfarin | AUC(0–inf) (ng h ml−1) | 16* | 19 760 (27) | 19 680 (25) | 1.00 | 0.95–1.06 |
| Cmax (ng ml−1) | 19 | 641 (22) | 650 (24) | 1.01 | 0.95–1.07 | |
| t1/2 (h) | 19 | 31.1 (26) | 31.9 (20) | NC | NC | |
| Omeprazole | AUC(0–inf) (ng h ml−1) | 17† | 2040 (127) | 1810 (97) | 1.00 | 0.88–1.13 |
| Cmax (ng ml−1) | 18 | 745 (68) | 785 (70) | 1.08 | 0.82–1.43 | |
| t1/2 (h) | 17† | 1.22 (72) | 1.12 (64) | NC | NC | |
| Caffeine | AUC0–12 (ng h ml−1)‡ | 12§ | 32 350 (37) | 36 110 (43) | 1.03 | 0.93–1.14 |
| Cmax (ng ml−1) | 12§ | 4734 (29) | 5352 (30) | 1.11 | 1.00–1.23 | |
| t1/2 (h)‡ | NC | NC | NC | NC | NC | |
| Dextromethorphan | 12‐h urine dextromethorphan to dextrorphan ratio | 20 | 0.425 (296)¶ | 0.489 (370)¶ | 1.01 | 0.76–1.34 |
%CV, coefficient of variation; AUC0–12, area under the curve from 0–12 h; AUC(0–inf), area under the curve from 0 to infinity; CI, confidence interval; Cmax, maximum concentration; CYP, cytochrome P450; DAC HYP, daclizumab high‐yield process; NC, not calculated; PK, pharmacokinetics; SC, subcutaneous; t1/2, terminal elimination half‐life.
AUC(0–inf) values extrapolated by >20% were excluded from the analysis.
Two patients with uncharacterizable terminal elimination phase and hence no AUC(0–inf) and t1/2 determined.
Caffeine AUC(0–inf) and t1/2 not reportable due to caffeine concentrations in most patients rebounded at or after 24 h post dose, which is probably due to ingestion of caffeinated drinks or food as patients were discharged 12 h post dose.
Seven patients in periods 1 and 2 had predose caffeine concentrations >5% of Cmax and data from these patients were excluded from all PK and statistical analysis.
High %CV due to three patients with poor metabolizer status for CYP2D6.