TABLE 3

Pharmacokinetic variables determined in bile for TI to TIV

All parameters are presented 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 into the jejunum. One hour before the administration of the rosuvastatin dose in TII, a cyclosporine infusion was started and continued for 2 h into the central vein catheter (total dose 300 mg). In TIII, 600 mg of gemfibrozil was administered as a bolus dose into the jejunum 20 min before rosuvastatin was given. In TIV, a single bolus dose of 5.9 mg of rosuvastatin was administered into the right ear vein. The biliary concentrations of rosuvastatin and gemfibrozil were determined using LC-MS/MS analysis. The biliary concentration of cyclosporine was not determined.

Rosuvastatin
Gemfibrozil (TIII)
TITIITIIITIV
Tmax (min)a60 (40–100)40 (20–40)40 (40–80)20100 (40–120)
Cmax (μM)385 ± 144209 ± 57.7*252 ± 163347 ± 1883.38 ± 1.73
AUC0–5 h (h·μM)580 ± 179271 ± 42.5***357 ± 118*118 ± 65.57.24 ± 3.77
AUCbile/AUCVP ratioa280 (185–342)73.0 (58.5–132)**157 (109–396)2260 (805–3270)0.04 ± 0.01
AUCbile/AUCVH ratioa1770 (1640–11300)138 (75.6–281)*888 (303–2810)4900 (1520–14400)0.05 ± 0.01
CLbile (ml/min/kg)4.21 ± 1.641.85 ± 0.82*5.02 ± 3.2446.5 ± 21.8N.D.
fe, bile (% of dose)9.0 ± 3.55.4 ± 1.2*9.3 ± 3.334.7 ± 15.60.014 ± 0.009
Biliary flow (ml/min)0.46 ± 0.170.64 ± 0.150.78 ± 0.360.48 ± 0.11
  • N.D., not determined.

  • * P < 0.05.

  • ** P < 0.01.

  • *** P < 0.001.

  • a Expressed as the median value and range.