Table 2

Pharmacokinetic parameters of lactone and carboxylate forms of SN-38 after i.v. administration of CPT-11 (10 and 40 mg/kg) in SD rats and EHBR

		Lactone Form		Carboxylate Form
		10 mg/kg	40 mg/kg	10 mg/kg	40 mg/kg
SD rats
AUC_(0–8hr)	(μg · hr/ml)	0.100 ± 0.009	0.209 ± 0.032	0.0474 ± 0.0081	0.249 ± 0.064
X _liver(8hr)	(μg/g liver)	0.0293 ± 0.0056	0.239 ± 0.077	0.0487 ± 0.0073	0.207 ± 0.045
X _bike(0-8hr)	(mg/kg)	0.0140 ± 0.0011	0.0196 ± 0.0035	0.207 ± 0.053	0.191 ± 0.049
CL _bile,p	(ml/min/kg)	2.43 ± 0.38	1.53 ± 0.05	72.0 ± 10.1	15.5 ± 5.3^**
CL _bile,h	(ml/min/kg)	0.440 ± 0.173	0.123 ± 0.034	5.46 ± 0.92	1.92 ± 0.97^*
C _bile/C _liver		10.1 ± 6.0	4.05 ± 0.66	118 ± 26	52.6 ± 12.5^*
X _{urine(0–8hr)}	(mg/kg)	0.0738 ± 0.0063	0.142 ± 0.035	0.0338 ± 0.0083	0.0229 ± 0.0053
CL _r	(liter/kg · hr)	0.754 ± 0.092	0.740 ± 0.105	0.784 ± 0.213	0.109 ± 0.032^*
EHBR
AUC_(0–8hr)	(μg · hr/ml)	0.117 ± 0.005	0.152 ± 0.012	0.339 ± 0.078	0.245 ± 0.060
X _liver(8hr)	(μg/g liver)	0.0700 ± 0.0020	0.0558 ± 0.0024	0.268 ± 0.012	0.171 ± 0.019
X _{bile(0–8hr)}	(mg/kg)	0.0110 ± 0.0025	0.0192 ± 0.0031	0.104 ± 0.026	0.256 ± 0.062
CL _bile,p	(ml/min/kg)	1.61 ± 0.38	2.09 ± 0.22	7.1 ± 1.5^‡	24.5 ± 10.9
CL _bile,h	(ml/min/kg)	0.183 ± 0.038	0.453 ± 0.136^*	0.553 ± 0.121^‡	2.57 ± 0.91^*
C _bile/C _liver		4.10 ± 2.05	13.3 ± 1.7^** ^‡	11.6 ± 6.2^‡	68.9 ± 10.3^*
X _{urine(0–8hr)}	(mg/kg)	0.0485 ± 0.0197	0.0715 ± 0.0159	0.0799 ± 0.0152	0.0543 ± 0.0175
CL _r	(liter/kg · hr)	0.398 ± 0.158	0.496 ± 0.128	0.242 ± 0.010^†	0.224 ± 0.075

All values are given as the mean ± S.E. of three different experiments.

* P < .05, ** P < .01, significantly different from 10 mg/kg dose, using Dunnett’s test.
† P < .05, ‡ P < .01, significantly different from SD rats, using Dunnett’s test.