Table 2.
40 mg atorvastatin | 40 mg + itraconazole | 40 mg + rifampicin | 40 mg + dulaglutide | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Obs | Pred | Pred/Obs | Obs ratio | Pred ratio | Pred/Obs | Obs ratio | Pred ratio | Pred/Obs | Obs ratio | Pred ratio | Pred/Obs | |
Atorvastatin | ||||||||||||
AUC (ng/mL • hour) | 54.2–99 | 78.6 (48) | 0.79–1.45 | 3.3 | 2.56 (2.47–2.67) | 0.78 | 7.3 | 7.66 (7.20, 8.15) | 1.05 | 0.786 (0.752, 0.821) | 0.758 (0.736–0.780) | 0.96 |
Cmax (ng/mL) | 12.7–19.5 | 18.2 (49) | 0.93–1.43 | 1.2 | 1.33 (1.30–1.35) | 1.1 | 10.5 | 9.42 (9.03–9.84) | 0.90 | 0.296 (0.246, 0.355) | 0.22 (0.21–0.23) | 0.74 |
Tmax (hour) | 0.5–1 | 0.72 (0.36–1.08) | 0.72–1.44 | — | — | — | — | — | — | 2.5 | 1.08 | 0.43 |
O‐hydroxyatorvastatin | ||||||||||||
AUC (ng/mL • hour) | 77.5–102 | 93.5 (52) | 0.92–1.21 | 0.83 | 0.85 (0.81–0.89) | 1.02 | — | — | — | 0.937 (0.887, 0.990) | 0.941 (0.916–0.965) | 1 |
Cmax (ng/mL) | 7.7–14.4 | 11.9 (48) | 0.83–1.55 | 0.17 | 0.22 (0.21–0.23) | 1.3 | — | — | — | 0.393 (0.330, 0.467) | 0.361 (0.336–0.388) | 0.92 |
Tmax (hour) | 1–3 | 1.26 (1.08–2.16) | 0.42–1.26 | — | — | — | — | — | — | 5 | 1.8 | 0.36 |
Atorvastatin lactone | ||||||||||||
AUC (ng/mL • hour) | 50.7–78.2 | 64.4 (47) | 0.82–1.27 | 4.0 | 3.44 (3.26–3.63) | 0.68 | — | — | — | — | — | — |
Cmax (ng/mL) | 3.8–8 | 3.75 (60) | 0.47–0.99 | 2.3 | 2.78 (2.64–2.92) | 1.2 | — | — | — | — | — | — |
Tmax (hour) | 2–3 | 1.93 (1.03–3.86) | 0.64–0.97 | — | — | — | — | — | — | — | — | — |
O‐hydroxy atorvastatin lactone | ||||||||||||
AUC (ng/mL • hour) | 128–187 | 162 (39) | 0.87–1.27 | 0.71 | 1.18 (1.14–1.21) | 1.7 | — | — | — | — | — | — |
Cmax (ng/mL) | 10.5–14.5 | 7.3 (50) | 0.50–0.70 | 0.29 | 0.61 (0.58–0.64) | 2.1 | — | — | — | — | — | — |
Tmax (hour) | 3–4 | 2.25 (1.2–9.33) | 0.56–0.75 | — | — | — | — | — | — | — | — | — |
Data for atorvastatin alone are from five studies reporting all four major atorvastatin‐related species.1, 2, 3, 5 Observed mean values are the means from all studies, predicted values for AUC and Cmax are the reported as geometric mean (CV%), and the predicted Tmax is reported as median (range). Data for atorvastatin with itraconazole, rifampicin, and dulaglutide are from single studies with each inhibitor.1, 3, 14 Observed ratio values are reported means or geometric means (90% confidence interval) in the case of dulaglutide, predicted values for AUC and Cmax ratios are geometric means (90% confidence interval), predicted Tmax ratio is reported as median difference (presence ‐absence of dulaglutide). AUC, area under the plasma concentration‐time curve; Cmax, maximum plasma concentration; Obs, observed; Pred, predicted; Tmax, time to maximum plasma concentration.