Table 3.
Predicted and Observed AUC(0‐∞) and Cmax Ratios for Abemaciclib, M2, M20, M18, and Active Species When Abemaciclib Is Coadministered With Clarithromycin and Rifampin
| Compound | Parameter | Observed Geometric Mean (90%CI) | Predicted Geometric Mean (90%CI) | Observed/Predicted |
|---|---|---|---|---|
| 50 mg abemaciclib with clarithromycin | ||||
| Abemaciclib | AUC(0‐∞) ratio | 3.37 (2.85‐3.99) | 3.80 (3.50‐4.11) | 0.89 |
| Cmax ratio | 1.30 (1.10‐1.52) | 1.61 (1.56‐1.66) | 0.81 | |
| M2 | AUC(0‐∞) ratio | 1.32 (1.14‐1.53) | 0.90 (0.85‐0.95) | 1.47 |
| Cmax ratio | 0.33 (0.27‐0.40) | 0.33 (0.30‐0.37) | 1.00 | |
| M20 | AUC(0‐∞) ratio | 0.94 (0.84‐1.06) | 1.32 (1.24‐1.41) | 0.71 |
| Cmax ratio | 0.27 (0.21‐0.34) | 0.47 (0.43‐0.51) | 0.57 | |
| M18 | AUC(0‐∞) ratio | NCa | 0.31 (0.28‐0.34) | NC |
| Cmax ratio | NCa | 0.13 (0.11‐0.15) | NC | |
| Potency‐adjusted unbound active species | AUC(0‐∞) ratio | 2.45 | 2.47 | 0.99 |
| 200 mg abemaciclib with rifampin | ||||
| Abemaciclib | AUC(0‐∞) ratio | 0.05 (0.04‐0.06) | 0.08 (0.07‐0.09) | 0.63 |
| Cmax ratio | 0.08 (0.07‐0.09) | 0.15 (0.13‐0.17) | 0.53 | |
| M2 | AUC(0‐∞) ratio | 0.35 (0.32‐0.38) | 0.38 (0.35‐0.41) | 0.92 |
| Cmax ratio | 0.96 (0.81‐1.13) | 0.84 (0.78‐0.90) | 1.14 | |
| M20 | AUC(0‐∞) ratio | 0.20 (0.19‐0.22) | 0.20 (0.18‐0.22) | 1.00 |
| Cmax ratio | 0.64 (0.56‐0.73) | 0.52 (0.47‐0.57) | 1.23 | |
| M18 | AUC(0‐∞) ratio | 1.31 (1.18‐1.44) | 1.67 (1.59‐1.76) | 0.78 |
| Cmax ratio | 4.26 (3.42‐5.31) | 3.40 (3.18‐3.64) | 1.25 | |
| Potency‐adjusted unbound active species | AUC(0‐∞) ratio | 0.23 | 0.28 | 0.82 |
AUC(0‐∞) indicates area under the concentration‐time curve from 0 to infinity; Cmax, maximal concentration observed; NC, not calculated.
a
Concentration values of M18 after administration of clarithromycin were below the limit of quantitation of 1 ng/mL.