The maternal plasma exposure (AUC), systemic clearance (CL), and plasma fraction unbound (fu) of norbuprenorphine (NBUP) and norbuprenorphine-3-β-d-glucuronide (NBUP-G) in pregnant and nonpregnant mice
Data shown are means (95% confidence interval). The NBUP-G/NBUP plasma AUC ratios were calculated based on molar concentrations of NBUP and NBUP-G in the maternal plasma. Differences between the pharmacokinetic parameters were calculated by the nonparametric bootstrap method as described in Materials and Methods. Differences in the PK parameters between pregnant and nonpregnant mice with P values of <0.05 were considered statistically significant.
| PK Parameter | Pregnant | Nonpregnant | P |
|---|---|---|---|
| AUC0–∞ of NBUP (μg × min × ml−1) | 4.2 (3.0, 6.5) | 10.8 (6.0, 16.1) | <0.05 |
| AUC0–∞ of NBUP (μM × min) | 10.2 (7.3, 15.7) | 26.1 (14.5, 38.9) | <0.05 |
| CL of NBUP (ml × min−1) | 7.8 (5.1, 10.7) | 3.1 (2.0, 5.5) | <0.05 |
| AUC0–∞of NBUP-G (μg × min × ml−1) | 27.9 (23.0, 40.8) | 66.2 (43.2, 101.5) | <0.05 |
| AUC0–∞ of NBUP-G (μM × min) | 57.0 (47.0, 83.3) | 135.2 (88.2, 207.3) | <0.05 |
| NBUP-G/NBUP plasma AUC Ratio | 5.6 (5.3, 6.5) | 5.2 (5.0, 6.0) | >0.05 |
| fu of NBUP (%) | 11.1 (8.8, 13.4) | 17.2 (13.8, 20.6) | >0.05 |