Pharmacokinetic parameters of the carboxylate form, lactone form, and total forms (i.e., carboxylate form plus lactone form) of CPT-11, SN-38, and SN-38G in rats administered CPT-11 (10 mg/kg by i.v. bolus injection) without or with S-1 (10 mg/kg/day by p.o. administration once daily for 7 consecutive days)
All data are expressed as mean ± S.D., n = 5.
Parameters | Without S-1 | With S-1 | Percentage of Change | P Value | |
|---|---|---|---|---|---|
| CPT-11 | |||||
| Carboxylate form | Cmax (ng/ml) | 1172.4 ± 403.5 | 773.9 ± 239.0 | −34.0 | 0.094 |
| AUC (ng · h/ml) | 3347.9 ± 1148.3 | 1955.0 ± 920.9 | −41.6 | 0.067 | |
| Lactone form | C max | 6167.5 ± 1351.9 | 4838.4 ± 698.2 | −21.6 | 0.087 |
| AUC | 6953.4 ± 1684.1 | 5428.9 ± 1282.8 | −21.9 | 0.146 | |
| Total form | C max | 8363.3 ± 3178.1 | 5206.7 ± 821.7 | −37.7 | 0.064 |
| AUC | 11037.6 ± 1470.0 | 7383.9 ± 2160.1 | −33.1 | 0.014 | |
| SN-38 | |||||
| Carboxylate form | C max | 118.8 ± 65.0 | 112.4 ± 23.9 | −5.4 | 0.844 |
| AUC | 219.3 ± 26.8 | 236.2 ± 59.9 | 7.7 | 0.581 | |
| Lactone form | C max | 144.1 ± 15.8 | 100.7 ± 8.9 | −30.1 | <0.001 |
| AUC | 235.8 ± 43.6 | 156.2 ± 15.0 | −33.8 | 0.005 | |
| Total form | C max | 259.6 ± 63.9 | 203.0 ± 28.6 | −21.8 | 0.108 |
| AUC | 468.2 ± 74.8 | 390.4 ± 72.7 | −16.6 | 0.134 | |
| SN-38G | |||||
| Carboxylate form | C max | 75.0 ± 21.54 | 45.3 ± 19.5 | −39.6 | 0.051 |
| AUC | 244.0 ± 64.7 | 152.8 ± 68.5 | −37.4 | 0.062 | |
| Lactone form | C max | 216.3 ± 113.4 | 134.4 ± 27.1 | −37.9 | 0.155 |
| AUC | 410.8 ± 181.7 | 337.2 ± 82.3 | −17.9 | 0.433 | |
| Total form | C max | 232.4 ± 72.6 | 174.0 ± 41.0 | −25.1 | 0.156 |
|
| AUC | 644.1 ± 249.2 | 490.0 ± 146.7 | −23.9 | 0.268 |
The differences were analyzed statistically using Student's unpaired t test.