Table 4.
Statistical comparison of the serum PK for the CYP probe substrate metabolite to parent ratios following the administration of a single oral dose of probe cocktail as probes alone, and following treatment with two subcutaneous doses of tildrakizumab 200 mg
| Compound | PK | CYP probe alone (Period 1, Day 1) | CYP probe + tildrakizumab (Period 2, Day 57) | GMR (90% CI) for CYP probe + tildrakizumab/CYP probe alone | ||
|---|---|---|---|---|---|---|
| n | GM (95% CI) | n | GM (95% CI) | |||
| 1‐Hydroxymidazolam/Midazolam | AUC0–∞ (hr*ng ml−1)a | 16 | 0.285 (0.248, 0.326) | 15 | 0.250 (0.201, 0.310) | 0.88 (0.73, 1.05) |
| C max (ng ml−1)a | 0.331 (0.287, 0.382) | 0.290 (0.233, 0.361) | 0.88 (0.73, 1.05) | |||
| 7‐Hydroxywarfarin/ S‐warfarin | AUC0–∞ (hr*ng ml−1)a | 12 | 0.209 (0.131, 0.333) | 11 | 0.211 (0.150, 0.297) | 1.01 (0.59, 1.73) |
| C max (ng ml−1)a | 19 | 0.101 (0.0861, 0.119) | 17 | 0.107 (0.0914, 0.125) | 1.06 (0.92, 1.22) | |
| Omeprazole | AUC0–∞ (hr*ng ml−1)a | 17 | 1440 (1020, 2040) | 15 | 1510 (1030, 2230) | 1.05 (0.83, 1.32) |
| C max (ng ml−1)a | 20 | 651 (489, 866) | 18 | 565 (464, 688) | 0.87 (0.69, 1.10) | |
| T max (h)b | 2.00 (1.50, 6.00) | 2.00 (1.00, 8.00) | ||||
| t 1/2 (h)c | 17 | 1.18 (43.9) | 15 | 1.06 (40.1) | ||
| Dextrorphan/Dextromethorphan | AUC0–∞ (hr*ng ml−1)a | 15 | 2.41 (1.45, 4.01) | 14 | 2.29 (1.31, 4.01) | 0.95 (0.81, 1.11) |
| C max (ng ml−1)a | 4.33 (2.73, 6.87) | 4.24 (2.53, 7.11) | 0.98 (0.82, 1.16) | |||
| Paraxanthine/Caffeine | AUC0–∞ (hr*ng ml−1)a | 11 | 1.03 (0.899, 1.17) | 8 | 1.08 (0.833, 1.40) | 1.05 (0.85, 1.30) |
| C max (ng ml−1)a | 19 | 0.393 (0.339, 0.456) | 17 | 0.440 (0.372, 0.520) | 1.12 (0.98, 1.27) | |
Back‐transformed least squares mean and confidence interval from linear mixed effects model performed on natural log‐transformed values
Median (min, max) reported for T max
Geometric mean and percent geometric CV reported for apparent terminal t 1/2
CYP, cytochrome P450; GM, geometric least‐squares mean; GMR, geometric least‐squares mean ratio; CI, confidence interval
Midazolam alone: A single oral dose of 2 mg midazolam
S‐warfarin alone: A single oral dose of 10 mg S‐warfarin
Dextromethorphan alone: A single oral dose of 30 mg dextromethorphan
Caffeine alone: A single oral dose of 200 mg caffeine