Dose of PSC 833 | ||||
---|---|---|---|---|
Control | 0.1 mg/kg | 0.3 mg/kg | 3 mg/kg | |
AUC0–120 min (Fd × min/ml) | 0.0511 ± 0.0031 | 0.0393 ± 0.0011-150 | 0.0594 ± 0.0027 | 0.0978 ± 0.0051-160 |
Xliver,120 min (Fd/g liver) | 0.000980 ± 0.000013 | 0.000870 ± 0.0003 | 0.00118 ± 0.00008 | 0.000858 ± 0.00015 |
Xbile,0–120 min(Fd) | 0.426 ± 0.058 | 0.410 ± 0.084 | 0.391 ± 0.083 | 0.213 ± 0.014 |
Xurine,0–120 min(Fd) | 0.0800 ± 0.0129 | 0.0673 ± 0.0055 | 0.0955 ± 0.0021 | 0.0907 ± 0.0017 |
CLbile(ml/min/kg) | 33.1 ± 2.73 | 46.3 ± 9.1 | 26.6 ± 5.8 | 8.77 ± 0.771-150 |
CLR (ml/min/kg) | 4.61 ± 0.49 | 4.24 ± 0.32 | 4.89 ± 0.18 | 3.23 ± 0.291-150 |
[3H]VCR was administered i.v. to rats that had received an i.v. injection of PSC 833 (0, 0.1, 0.3, and 3 mg/kg) 30 min before the experiments. Amount of [3H]VCR in the plasma, bile, and urine specimens was determined with HPLC. The plasma concentration-time profiles of [3H]VCR are shown in Fig. 1. Kinetic parameters were calculated as described in the text. Xliver represents the fraction of administered dose (Fd) associated with 1 g liver at 2 h after administration. Results are given as the mean ± S.E. of three independent experiments.