Table 1

Pharmacokinetic parameters for [³H]PSC 833 after iv administration

		0.1 mg/kg PSC 833	0.3 mg/kg PSC 833	3 mg/kg PSC 833	10 mg/kg PSC 833	30 mg/kg PSC 833
AUC_0–180min	(Fd × min/ml)	0.092 ± 0.009	0.098 ± 0.005	0.146 ± 0.008^1-a	0.151 ± 0.015^1-a	0.126 ± 0.034
X _{liver(0–180min)}	(Fd/g of liver)	0.00712 ± 0.00045	0.00559 ± 0.00076	0.00387 ± 0.00043	0.00410 ± 0.00059	0.00931 ± 0.00300
X _{bile(0–180min)}	Fd	0.0114 ± 0.0007	0.0110 ± 0.0007	0.00970 ± 0.00090	0.00775 ± 0.00061^1-b	0.00313 ± 0.00109^1-b
CL _bile	(ml/min/kg)	0.510 ± 0.052	0.457 ± 0.050	0.263 ± 0.012^1-c	0.215 ± 0.037^1-b	0.117 ± 0.048^1-b
CL _R	(ml/min/kg)	ND^1-d	ND	ND	ND	ND
X _{liver,total(180min)}	(Fd/g of liver)	0.0166 ± 0.0012	0.0124 ± 0.0006	0.00985 ± 0.00010	0.00886 ± 0.00100	0.0177 ± 0.0045
X _{bile,total(0–180min)}	Fd	0.308 ± 0.009	0.283 ± 0.017	0.384 ± 0.026^1-a	0.256 ± 0.021	0.069 ± 0.031^1-b
X _{urine,total(0–180min)}	Fd	0.0081 ± 0.0012	0.0075 ± 0.0010	0.0128 ± 0.0015	0.0179 ± 0.0036^1-a	0.0066 ± 0.0028

[³H]PSC 833 was given iv to rats at doses of 0.1, 0.3, 3, 10, and 30 mg/kg. Amounts of [³H]PSC 833 in the blood, bile, and urine were determined by HPLC. The blood concentration-time profiles for [³H]PSC 833 are indicated in fig. 1. Pharmacokinetic parameters were calculated using the method described in the text. X_liver represents the fraction of administered dose (Fd) associated with 1 g of liver at 3 hr after administration. X_bile,total andX_urine,total represent the total radioactivity excreted into bile and urine, respectively. Results are given as the mean ± SE of four independent experiments.
↵1-a p < 0.05, significantly different from 0.1 mg/kg dose by Fisher t test.
↵1-b p < 0.01.
↵1-c p < 0.001.
↵1-d ND, not detectable.