Table 1

Pharmacokinetic parameters of [³H]VCR after i.v. administration to rats

	Dose of PSC 833
	Control	0.1 mg/kg	0.3 mg/kg	3 mg/kg
AUC_{0–120 min} (Fd × min/ml)	0.0511 ± 0.0031	0.0393 ± 0.001^1-150	0.0594 ± 0.0027	0.0978 ± 0.005^1-160
X_{liver,120 min} (Fd/g liver)	0.000980 ± 0.000013	0.000870 ± 0.0003	0.00118 ± 0.00008	0.000858 ± 0.00015
X_{bile,0–120 min}(Fd)	0.426 ± 0.058	0.410 ± 0.084	0.391 ± 0.083	0.213 ± 0.014
X_{urine,0–120 min}(Fd)	0.0800 ± 0.0129	0.0673 ± 0.0055	0.0955 ± 0.0021	0.0907 ± 0.0017
CL_bile(ml/min/kg)	33.1 ± 2.73	46.3 ± 9.1	26.6 ± 5.8	8.77 ± 0.77^1-150
CL_R (ml/min/kg)	4.61 ± 0.49	4.24 ± 0.32	4.89 ± 0.18	3.23 ± 0.29^1-150

[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. X_liver 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.

↵1-150 P < .05, significantly different from control, using Fisher’s t test.
↵1-160 P < .01, significantly different from control, using Fisher’s t test.