Biliary and intestinal secretion of parent drug and metabolites by wild-type1 and mdr1a(−/−) mice2 with a cannulated gallbladder within 90 min after i.v. bolus administration of 5 mg/kg doxorubicin
| Doxorubicin | Doxorubicinol | 7-Deoxydoxorubicinolone | 7-Deoxydoxorubicinone | |||||
|---|---|---|---|---|---|---|---|---|
| Wild-type | mdr1a(−/−) | Wild-type | mdr1a(−/−) | Wild-type | mdr1a(−/−) | Wild-type | mdr1a(−/−) | |
| Plasma | 150 ± 22 | 166 ± 23 | 23.9 ± 4.6 | 23.0 ± 2.6 | 17.6 ± 8.4 | 38.8 ± 12.0 | 7.4 ± 0.3 | 8.9 ± 3.3 |
| Bile | 13.3 ± 1.7 | 2.4* ± 0.3 | 0.53 ± 0.09 | 0.20*± 0.05 | <0.01 | <0.01 | <0.01 | <0.01 |
| Contents of: | ||||||||
| small | 10.0 ± 0.6 | 9.6 ± 0.4 | <0.01 | <0.01 | 0.18 ± 0.04 | 0.66 ± 0.38 | 0.12 ± 0.04 | 0.11 ± 0.02 |
| intestine | ||||||||
| cecum | 0.11 ± 0.02 | 0.16 ± 0.03 | <0.01 | <0.01 | 0.04 ± 0.01 | <0.01 | 0.01 ± 0.00 | 0.01 ± 0.00 |
| colon | 0.34 ± 0.15 | 0.25 ± 0.08 | <0.01 | <0.01 | 0.06 ± 0.01 | <0.01 | 0.02 ± 0.00 | <0.01 |
| total intestine | 10.5 ± 0.5 | 10.0 ± 0.4 | <0.01 | <0.01 | 0.22 ± 0.05 | 0.66 ± 0.38 | 0.15 ± 0.05 | 0.12 ± 0.02 |
Data (means ± S.E.) are represented as a percentage of the administered dose (plasma concentration at t = 90 min in nM); * P < .05 versus wild-type mice (1n = 7; 2n = 8).