Pharmacokinetic parameters of topotecan in SD rats after oral administration of topotecan (2 mg/kg) either alone or with GF120918, chrysin, and BF
The plasma concentration-time profile of topotecan in SD rats after oral coadministration of topotecan (2 mg/kg) with glycofurol (control) or the specified doses of the test compounds was determined as described under Materials and Methods. The pharmacokinetic parameters were obtained by noncompartmental analysis using WinNonlin. Data are expressed as mean ± S.D. The number of animals for various treatment groups is specified in parentheses after the corresponding group names.
Parameters | Control (n = 7) | GF120918 (50 mg/kg) (n = 4) | Chrysin | BF | ||||
|---|---|---|---|---|---|---|---|---|
| 5 mg/kg (n = 3) | 50 mg/kg (n = 6) | 10 mg/kg (n = 9) | 50 mg/kg (n = 8) | |||||
| AUC0-720 (× 104 ng/ml · min) | 1.74 ± 0.86 | 7.65 ± 3.78** | 1.29 ± 0.24 | 0.88 ± 0.83 | 2.04 ± 0.48 | 2.50 ± 1.14 | ||
| AUC0-∞ (× 104 ng/ml · min) | 1.80 ± 0.89 | 7.91 ± 3.56** | 1.34 ± 0.27 | 0.93 ± 0.85 | 2.15 ± 0.43 | 2.57 ± 1.15 | ||
| Cmax (ng/ml) | 86.4 ± 42.9 | 257 ± 154* | 68.3 ± 32.2 | 36.0 ± 37.9 | 98.0 ± 45.7 | 101 ± 42.9 | ||
| Tmax (min) | 52.0 ± 85.3 | 75.0 ± 30.0 | 35.0 ± 22.9 | 75.0 ± 82.2 | 82.4 ± 91.4 | 52.0 ± 50.9 | ||
| t1/2 (min) | 127 ± 20.0 | 167 ± 65.1 | 139 ± 40.4 | 173 ± 47.7 | 150 ± 63.6 | 127 ± 37.3 | ||
| Bioavailability (F) (%) | 29.7 ± 14.8 | 130 ± 58.8** | 22.1 ± 4.47 | 15.3 ± 14.1 | 35.5 ± 7.33 | 42.5 ± 7.09 | ||
↵* p < 0.05; **p < 0.01.