Table 4.
Pharmacokinetic parameters of CZ48 and active metabolite CPT from cosolvent, NS-S and NS-L after i.v. administration in mice (n=6)
| Parameters | Unit | Cosolvent (5 mg/kg) | NS-S (25 mg/kg) | NS-L (25 mg/kg) | |
|---|---|---|---|---|---|
| CZ48 | t1/2 | hrs | 0.70±0.13 | 8.00±1.03* | 5.58±1.20*# |
| C0/Dose | nM/(mg/kg) | 381.66±105.31 | 122.29±40.14 | 172.48±34.39* | |
| Vss | L/kg | 6.48±2.46 | 41.12±11.85* | 30.61±12.28*# | |
| CL | L/kg*hr | 6.41±1.82 | 9.03±2.82* | 10.19±3.47*# | |
| AUC0-∝/Dose | nM*hr/(mg/kg) | 385.70±81.95 | 440.08±54.10 | 362.95±63.52*# | |
| Fab | 1.14 | 0.94 | |||
| CPT | t1/2 | hrs | 0.40±0.10 | 12.51±2.86* | 5.81±1.71*# |
| t1/2ka | hrs | 0.06±0.03 | 0.47±0.18 | 0.50±0.22 | |
| Vss | L/kg | 11,587±2143 | 10,570±4093 | 7209±1466 | |
| CL | L/kg*hr | 19,894±4300 | 2383±753.7* | 3758±780.3*# | |
| Tmax | hrs | 0.20±0.04 | 0.67±0.10* | 0.75±0.15* | |
| Cmax/Dose | nM/(mg/kg) | 10.12±2.13 | 7.38±1.99* | 4.46±1.10 | |
| AUC0-∝/Dose | nM*hr/(mg/kg) | 8.29±3.45 | 19.78±6.94* | 10.95±1.33*# | |
| Fab | 2.39 | 1.32 |
Notes: *p<0.05 compared to that of cosolvent by t-test; #p<0.05 compared to that of NS-S by t-test.
Abbreviations: CPT, camptothecin; NS-L, CZ48 nanosuspension with particle size of 589.35 ± 23.27 nm; NS-S, CZ48 nanosuspension with particle size of 197.22 ± 7.12 nm; i.v., intravenous.