Concentrations of triazolam and ketoconazole in control mice and in mdr1a(-) mice Values are mean (±S.E.) (n = 3 per group). Administered doses were: KET, 50 mg/kg, attime zero, followed by TRZ, 0.175 mg/kg 15 min later. Animals were sacrificed 15 min after TRZ dosage (30 min after KET dosage).
FVB Controls | mdr1a(–) | |||||
|---|---|---|---|---|---|---|
| TRZ | TRZ + KET | TRZ | TRZ + KET | |||
| Triazolam concentrations | ||||||
| Serum (ng/ml) | 12.7 (±5.2)a | 33.1 (±2.0)a | 8.7 (±0.2)a | 34.0 (±5.7)a | ||
| Brain (ng/g) | 96 (±12) | 213 (±44) | 92 (±21)a | 192 (±15)a | ||
| Liver (ng/g) | 255 (±63) | 451 (±148) | 161 (±41)a | 697 (±181)a | ||
| Brain/serum ratio | 9.3 (±2.3) | 6.4 (±1.3) | 10.5 (±2.3) | 5.8 (±0.6) | ||
| Liver/serum ratio | 22.6 (±3.1) | 13.4 (±4.1) | 18.3 (±4.4) | 21.5 (±6.8) | ||
| KET | KET + TRZ | KET | KET + TRZ | |
|---|---|---|---|---|
| Ketoconazole concentrations | ||||
| Serum (μg/ml) | 30.2 (±8.3) | 26.1 (±4.1) | 32.1 (±1.7) | 34.7 (±6.2) |
| Liver (μg/g) | 39.9 (±6.8) | 45.3 (±4.2) | 52.3 (±5.7) | 50.6 (±2.8) |
| Liver/serum ratio | 1.8 (±0.9) | 1.8 (±0.4) | 1.6 (±0.1) | 1.5 (±0.2) |
↵ a p < 0.05 for comparison of mean values for TRZ group vs. TRZ + KET group