Predicted changes in atorvastatin exposure (AUC) during coadministration with fibrates
Fibrate | Drug Concentrationa | Predicted AUC Change | Observed AUC Changeb | |
|---|---|---|---|---|
| μM | -fold | |||
| Gemfibrozil (600 mg twice daily) | 1.24-1.35 | |||
| Plasma Cmax (total) | 82 | 1.34 | ||
| Plasma Cmax (unbound) | 1.6 | 1.01 | ||
| Portal vein (unbound) | 41 | 1.18 | ||
| Fenofibrate (160 mg daily) | 1.03 | |||
| Plasma Cmax (total) | 27 | 1.13 | ||
| Plasma Cmax (unbound) | 0.27 | 1.00 | ||
| Portal vein (unbound) | 3.7 | 1.02 |
| |
↵ a Fibrate plasma concentration values were obtained from literature values (Whitfield et al., 2005). Unbound fraction (fu) for gemfibrozil and fenofibrate was 0.02 and 0.01, respectively.
↵ b Clinically observed changes in atorvastatin AUC after coadministration of fibrates were previously reported (Backman et al., 2005; Whitfield et al., 2005).