Table 3.
Statistical comparison of primary R- and S-warfarin pharmacokinetic and pharmacodynamic parameters following co-administration of warfarin 25 mg and fostamatinib (100 mg twice daily)
| Analyte | Parameter (units) | Treatment | n | Geometric LS mean | Warfarin + fostamatinib/warfarin alone | |
|---|---|---|---|---|---|---|
| Ratio (%) | 90 % CI | |||||
| R-Warfarin | AUC (ng·h/mL) | Warfarin alone | 11 | 65,228 | ||
| Warfarin + fostamatinib | 11 | 76,828 | 117.8 | 113.0–122.7 | ||
| C max (ng/mL) | Warfarin alone | 13 | 1177 | |||
| Warfarin + fostamatinib | 13 | 1202 | 102.1 | 97.0–107.5 | ||
| S-Warfarin | AUC (ng·h/mL) | Warfarin alone | 14 | 43,014 | ||
| Warfarin + fostamatinib | 14 | 48,528 | 112.8 | 107.4–118.5 | ||
| C max (ng/mL) | Warfarin alone | 14 | 1188 | |||
| Warfarin + fostamatinib | 14 | 1173 | 98.7 | 91.5–106.4 | ||
| INR | INRmax | Warfarin alone | 14 | 1.65 | ||
| Warfarin + fostamatinib | 14 | 1.48 | 89.7 | 84.6–95.2 | ||
| AUCINR,0–168 (h) | Warfarin alone | 14 | 206.65 | |||
| Warfarin + fostamatinib | 14 | 200.44 | 97.0 | 95.3–98.8 | ||
Results based on analysis of variance model on log-transformed pharmacokinetic parameters with fixed effects for treatment and subject
AUC area under the plasma concentration–time curve extrapolated to infinity, AUC INR,0–168 area under the INR time curve from zero to 168 h post-dose, CI confidence interval, C max maximum plasma concentration, INR international normalized ratio, INR max maximum INR, LS least-squares