Comparison of predicted and observed DDI data (AUC and Cmax ratio)
The predicted AUC or Cmax ratio is reported as the geometric mean ratio with 90% confidence interval in parentheses; the observed AUC or Cmax ratio is the mean AUC or Cmax ratio. The AUC for simvastatin and metoprolol is AUC0-24, and for wafarin is AUC0-last.
| AUC Ratio | Cmax Ratio | |
|---|---|---|
| Warfarin +/−AMIO (300 mg QD1 or 200 mg BID2) | ||
| Predicted | ||
| AMIO comp. inh. | No interaction | No interaction |
| AMIO comp. inh. + TDI, MDEA comp. inh. | 1.14 (1.13–1.15)1 | 1.01 (1.01–1.02)1 |
| 1.18 (1.16–1.19) 2 | 1.02 (1.01–1.02) 2 | |
| Observed (O’reilly et al., 1987; Heimark et al., 1992) | 1.271 | N/A |
| 2.112 | N/A | |
| Simvastatin +/− AMIO (400 mg, QD) | ||
| Predicted | ||
| AMIO comp. inh. | No interaction | No interaction |
| AMIO comp. inh. + MDEA comp. inh. | 1.93 (1.86–2.01) | 1.93 (1.8–2.0) |
| Observed (Becquemont et al., 2007) | 1.73 | 2.0 |
| Metoprolol +/− AMIO (1200 mg, QD) | ||
| Predicted | ||
| AMIO comp. inh. | No interaction | No interaction |
| AMIO comp. inh., MDEA comp. inh. +TDI | 2.45 (2.25–2.66) | 1.53 (1.46–1.59) |
| Observed (Werner et al., 2004) | 1.97 | 2.0 |
AUC ratio, AUC in the presence of inhibitor/AUC in the absence of inhibitor; AUC0–24, area under the curve from zero to 24 hours; AUC0–last, area under the curve from zero to the last time point; Cmax ratio, Cmax in the presence of inhibitor/Cmax in the absence of inhibitor; comp. inh., competitive inhibition; N/A, not available.