Table 2.
Ratios of rosuvastatin maximum concentration and area under the curve when coadministered with inhibitors vs. administered alone
| Rosuvastatin dose/frequency | Inhibitor, dose/frequency | Transporters inhibited | Cmax | AUC | |
|---|---|---|---|---|---|
| 10 mg q.d. | Cyclosporine, 200 mg p.o., b.i.d. | OATP1B1/3, BCRP, NTCP | Observed ratioa | 10.6 | 7.1 |
| Median ratios from simulated trials (range of mean ratios) | 7.14 (5.26–9.43) | 5.07 (3.92–6.96) | |||
| 5 mg single dose | Rifampin, 600 mg p.o., single dose | OATP1B1/3, BCRP | Observed GMR (90% CI)b | 9.93 (7.25–13.6) | 5.24 (3.66–7.49) |
| Median ratios from simulated trials (range of mean ratios) | 8.49 (6.35–11.1) | 6.58 (5.00–8.49) | |||
| 5 mg single dose | Rifampin, 600 mg i.v., single dose | OATP1B1/3, BCRP | Observed GMR (90% CI)b | 5.51 (4.38–6.93) | 3.30 (2.42–4.50) |
| Median ratios from simulated trials (range of mean ratios) | 4.05 (3.08–4.90) | 3.64 (2.86–4.37) | |||
| 80 mg single dose | Gemfibrozil, 600 mg p.o., b.i.d. | OATP1B1, OAT3 | Observed GMR (90% CI)c | 2.21 (1.81–2.69) | 1.88 (1.60–2.21) |
| Median ratios from simulated trials (range of mean ratios) | 2.04 (1.87–2.25) | 1.79 (1.69–1.97) |
AUC, area under the curve; BCRP, breast cancer resistance protein; CI, confidence interval; Cmax, maximum concentration; GMR, geometric mean ratio; NTCP, sodium‐taurocholate co‐transporting polypeptide; OAT3, organic anion‐transporting 3; OATP, organic anion‐transporting polypeptide.
Data from Simonson et al.28 2004: 10 mg rosuvastatin was administered to patients with heart failure, and the AUC and Cmax ratios were obtained by comparing with data from a study in healthy volunteers. bData from Prueksaritanont et al.29 2014: 5 mg rosuvastatin was administered to healthy volunteers in the presence or absence of rifampin. cData from Schneck et al.30 2004: 80 mg rosuvastatin was dosed to healthy volunteers in the presence or absence of gemfibrozil.