Table 3

Pharmacokinetic parameters of lactone and carboxylate forms of SN38-Glu 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)0.826  ± 0.1843.63  ± 0.590.360  ± 0.0251.60  ± 0.41
X liver(8hr) (μg/g liver)0.189  ± 0.0040.245  ± 0.0560.0303  ± 0.00670.161  ± 0.052
X bile(0–8hr) (mg/kg)0.470  ± 0.0470.431  ± 0.1370.201  ± 0.0170.172  ± 0.037
CL bile,p (ml/min/kg)12.2  ± 4.22.07  ± 0.68* 9.30  ± 0.132.40  ± 0.99*
CL bile,h (ml/min/kg)3.38  ± 0.262.61  ± 0.9112.5  ± 2.62.67  ± 1.29*
C bile/C liver 74.1  ± 3.587.4  ± 31.7284  ± 11171.5  ± 10.6*
X urine(0–8hr) (mg/kg)0.211  ± 0.0520.713  ± 0.1050.0719  ± 0.01230.0516  ± 0.0039
CL r (liter/kg · hr)0.306  ± 0.0850.212  ± 0.0430.203  ± 0.0370.0385  ± 0.0093*
EHBR
 AUC(0–8hr) (μg · hr/ml)3.39  ± 0.194.13  ± 0.733.23  ± 0.153.03  ± 0.85
X liver(8hr) (μg/g liver)0.349  ± 0.0040.313  ± 0.0170.112  ± 0.0130.106  ± 0.040
X bile(0–8hr) (mg/kg)0.0699  ± 0.02350.168  ± 0.0690.0222  ± 0.00850.0516  ± 0.0220
CL bile,p (ml/min/kg)0.366  ± 0.136 0.768  ± 0.2940.115  ± 0.047 0.389  ± 0.189
CL bile,h (ml/min/kg)0.148  ± 0.062 1.16  ± 0.520.154  ± 0.063 0.738  ± 0.181*
C bile/C liver 5.95  ± 2.94 27.9  ± 10.3 6.16  ± 2.54 22.3  ± 2.1
X urine(0–8hr) (mg/kg)0.477  ± 0.0830.643  ± 0.1090.186  ± 0.0120.234  ± 0.073
CL r (liter/kg · hr)0.138  ± 0.0570.182  ± 0.0610.0577  ± 0.0045 0.0859  ± 0.0342

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.