Biliary and intestinal secretion of parent drug and metabolites by wild-type and mdr1a(−/−) mice with a cannulated gallbladder within 90 min after i.v. bolus administration of 1 mg/kg [3H]vinblastine
| Vinblastine | Deacetylvinblastine | 3H label | ||||
|---|---|---|---|---|---|---|
| Wild-type | mdr1a(−/−) | Wild-type | mdr1a(−/−) | Wild-type | mdr1a(−/−) | |
| Plasma | 31.4 ± 7.1 | 23.4 ± 4.0 | 9.1 ± 1.5 | 6.6 ± 0.8 | n.a.2-a | n.a.2-a |
| Bile | 1.1 ± 0.2 | 0.38* ± 0.06 | 0.19 ± 0.02 | 0.12* ± 0.02 | 26.7 ± 1.3 | 28.9 ± 2.0 |
| Contents of: | ||||||
| small | 5.4 ± 0.7 | 2.8* ± 0.5 | 0.57 ± 0.04 | 0.29* ± 0.07 | 9.2 ± 0.4 | 6.4* ± 0.5 |
| intestine | ||||||
| cecum | 1.0 ± 0.1 | 0.14* ± 0.03 | 0.03 ± 0.00 | 0.02 ± 0.01 | 0.77 ± 0.08 | 0.13* ± 0.02 |
| colon | 0.37 ± 0.06 | 0.30 ± 0.06 | 0.02 ± 0.01 | 0.03 ± 0.01 | 0.42 ± 0.07 | 0.28 ± 0.06 |
| total intestine | 6.7 ± 0.7 | 3.3* ± 0.6 | 0.62 ± 0.04 | 0.39* ± 0.05 | 10.4 ± 0.4 | 6.8* ± 0.5 |
Data (means ± S.E.) are represented as a percentage of the administered dose (plasma concentration at t = 90 min in nanograms per milliliter); * P < .05 versus wild-type mice (n = 6 animals per group).
↵2-a n.a., not available.