Effect of BCRP inhibitor GF120918 on pharmacokinetics of topotecan in mdr 1a / 1b(-/-) mice (Jonker et al., 2000)
| Vehicle-Treated | GF120918-Treated | Ratio | |
|---|---|---|---|
| Oral administration of topotecan (1 mg/kg)a | |||
| AUC (mg · h/1) | 96 | 596 | ×6.2 |
| Intravenous administration of topotecan (1 mg/kg)a | |||
| AUC (mg · h/1) | 200 | 406 | ×2.0 |
| Biliary excretion b (%) | 14.7 | 5.5 | ×0.4 |
| Intestinal content of [14C]topotecan-derived radioactivityc | |||
| Intestinal (%) | 31.8 | 10.2 | ×0.3 |
| Plasma (ng/ml) | 40 | 102 | ×2.6 |
↵ a Mdr1a/1b(-/-) mice were given an oral dose of GF120918 (50 mg/kg) or vehicle 15 min before an oral or intravenous dose of topotecan (1 mg/kg).
↵ b Cumulative biliary excretion of unchanged topotecan for 11 min.
↵ c GF 120918 (50 mg/kg) was administered orally; 15 min later, [14C]topotecan (1 mg/kg) was administered intravenously; 60 min after administration of [14C]topotecan, the intestinal content of [14C] was determined.