Table 1

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

Lactone FormCarboxylate Form
10 mg/kg40 mg/kg10 mg/kg40 mg/kg
SD rats
 AUC(0–8hr) (μg · hr/ml)4.13  ± 0.3429.7  ± 0.93.39  ± 0.2345.6  ± 5.9
X liver(8hr) (μg/g liver)4.78  ± 1.2285.7  ± 9.50.342  ± 0.09013.5  ± 2.6
X bile(0–8hr) (mg/kg)1.25  ± 0.062.85  ± 0.451.96  ± 0.445.55  ± 1.26
CL bile,p (ml/min/kg)5.19  ± 0.611.61  ± 0.27* 9.70  ± 2.022.29  ± 0.75*
CL bile,h (ml/min/kg)0.0901  ± 0.00620.0454  ± 0.01604.00  ± 1.041.08  ± 0.59*
C bile/C liver 2.00  ± 0.232.12  ± 1.2985.8  ± 32.826.9  ± 4.7*
X urine(0–8hr) (mg/kg)1.97  ± 0.0211.2  ± 0.30.383  ± 0.0041.26  ± 0.03
CL r (liter/kg · hr)0.485  ± 0.0820.378  ± 0.0250.115  ± 0.0090.0289  ± 0.0036**
EHBR
 AUC(0–8hr) (μg · hr/ml)5.27  ± 0.0618.0  ± 0.913.8  ± 1.935.1  ± 7.5
X liver(8hr) (μg/g liver)12.9  ± 1.668.3  ± 21.63.16  ± 0.286.62  ± 2.80
X bile(0–8hr) (mg/kg)0.837  ± 0.1562.40  ± 0.271.27  ± 0.217.62  ± 0.98
CL bile,p (ml/min/kg)2.64  ± 0.472.20  ± 0.161.71  ± 0.45 4.33  ± 1.10
CL bile,h (ml/min/kg)0.0520  ± 0.01800.0353  ± 0.00960.240  ± 0.104 2.52  ± 0.85*
C bile/C liver 1.24  ± 0.751.06  ± 0.179.69  ± 5.7 64.0  ± 19.2*
X urine(0–8hr) (mg/kg)1.69  ± 0.165.69  ± 1.350.553  ± 0.1331.85  ± 0.58
CL r (liter/kg · hr)0.321  ± 0.1020.324  ± 0.0880.0386  ± 0.0055 0.0551  ± 0.0205

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.