Pharmacokinetic properties determined in plasma for rosuvastatin and gemfibrozil (TI, TII, and TIII) and in whole blood for cyclosporine (TII)
All parameters are given as arithmetic means and the variability is expressed as the S.D. unless otherwise stated. In TI, TII, and TIII, 80 mg of rosuvastatin was administered as an oral solution in the jejunum. Cyclosporine (300 mg) and gemfibrozil (600 mg) were administered concomitantly with rosuvastatin in TII and TIII, respectively. Rosuvastatin and gemfibrozil were analyzed using LC-MS/MS, and cyclosporine was analyzed by immunoassay.
| Rosuvastatin | Cyclosporine (TII) | Gemfibrozil (TIII) | |||
|---|---|---|---|---|---|
| TI | TII | TIII | |||
| Tmax (min)a | |||||
| VP | 40 (20–80) | 20 (–20)** | 20 (20–60) | 120 | 90 (20–140) |
| VH | 40 (20–60) | 20 (20–40)* | 40 (20–60) | 120 | 70 (20–140) |
| VF | 60 (40–100) | 20 (20–40)* | 40 (20–60) | N.D. | 90 (20–140) |
| Cmax (μM) | |||||
| VP | 1.60 ± 0.72 | 3.17 ± 1.28* | 1.69 ± 1.27 | 3.80 ± 0.72 | 84.1 ± 30.3 |
| VH | 0.15 ± 0.12 | 1.84 ± 1.00*** | 0.45 ± 0.50 | 3.60 ± 0.65 | 55.5 ± 17.8 |
| VF | 0.15 ± 0.08 | 1.24 ± 0.36*** | 0.44 ± 0.47 | N.D. | 61.5 ± 20.4 |
| AUC0–5 h (h·μM) | |||||
| VP | 2.22 ± 0.67 | 3.67 ± 1.45* | 2.30 ± 1.35 | 6.44 ± 1.55 | 190 ± 62.3 |
| VH | 0.27 ± 0.18 | 2.06 ± 1.27*** | 0.56 ± 0.60 | 6.10 ± 1.68 | 136 ± 58.6 |
| VF | 0.27 ± 0.11 | 1.59 ± 0.48*** | 0.65 ± 0.68 | N.D. | 160 ± 64.8 |
| Terminal half-life (h)a | |||||
| VP | 6.9 (0.5–22)b | 2.4 (1.1–2.8) | 2.3 (1.7–25) | N.D. | 0.8 (0.7–2.2) |
| VH | 4.2 (0.9–10)b | 1.4 (1.2–4.4) | 2.7 (0.4–7.8) | N.D. | 0.8 (0.8–2.2) |
| VF | 3.3 (0.7–65) | 1.7 (1.2–3.9) | 1.8 (1.4–21) | N.D. | 0.8 (0.7–2.2) |
| EH | 0.89 ± 0.06 | 0.46 ± 0.13*** | 0.80 ± 0.09 | 0.06 ± 0.10 | 0.30 ± 0.10 |
| CL/F (ml/min/kg) | 444 ± 303 | 75.4 ± 26.8* | 288 ± 278 | N.D. | N.D. |
| V/F (l/kg) | 91.5 ± 82.2b | 12.8 ± 7.27* | 25.2 ± 10.6b | N.D. | N.D. |