Table 5.
Fetal AUCs of norbuprenorphine (NBUP) and norbuprenorphine-3-β-D-glucuronide (NBUP-G) after retro-orbital injection (1 mg/kg) to pregnant mice on gd 15 over 480 min. Data are reported as mean (95% confidence interval). The NBUP-G/NBUP AUC ratios were calculated based on molar concentrations of NBUP and NBUP-G in the fetus. Differences between the analyte AUCs or the AUC ratios of wild-type and Abcb1a-/-/1b-/-or Abcb1a-/-/1b-/-/Abcg2-/- mice were calculated using bootstrapping as described in the Materials and methods section. The p values were corrected for multiple testing using the Bonferroni method.
| Parameter | Genotype | ||||
|---|---|---|---|---|---|
|
|
|||||
| Wild-type | Abcb1a/1b-/- | p | Abcb1a/1b;Abcg2-/- | p | |
| Fetal AUC0-480min of NBUP (μg×min×g-1) | 2.5 [2.0, 2.9] | 4.0 [3.5, 4.5] | < 0.005 | 4.1 [3.5, 4.6] | < 0.05 |
| Fold-change | 1.0 | 1.6 | 1.6 | ||
|
| |||||
| Fetal/Maternal plasma AUC ratio of NBUP | 0.64 [0.40, 0.83] | 0.56 [0.39, 0.63] | 1.0 | 0.45 [0.28, 0.60] | 0.6 |
| Fold-change | 1.0 | 0.87 | 0.71 | ||
|
| |||||
| Fetal AUC0-480min of NBUP-G (μg×min×g-1) | 189.2 [159.2, 199.2] | 314.5 [266.0, 363.1] | < 0.0001 | 373.5 [287.6, 485.1] | < 0.0001 |
| Fold-change | 1.0 | 1.7 | 2.0 | ||
|
| |||||
| Fetal/Maternal plasma AUC ratio of NBUP-G | 7.2 [4.8, 9.2] | 3.31 [2.1, 4.6] | 0.2 | 3.2 [2.0, 4.8] | 0.2 |
| Fold-change | 1.0 | 0.46 | 0.45 | ||
|
| |||||
| NBUP-G/NBUP fetal AUC ratio | 53.9 [53.9, 54.6] | 55.9 [46.4, 66.3] | 0.9 | 64.6 [50.2, 83.3] | 0.9 |
| Fold-change | 1.0 | 1 | 1.2 | ||