Pharmacokinetic parameters of glyburide in pregnant and nonpregnant FVB wild-type (WT) or Bcrp1(−/−) mice after retro-orbital administration at a dose of 1 mg/kg b.wt.
The pharmacokinetic parameters were estimated using Bailer's approach (Bailer, 1988). AUC, CL, MRT, T1/2, and Vss are presented as means ± S.E. (n = 3–5 mice per time point), and the fraction unbound fu (%) is presented as mean ± S.D. of 3 to 5 independent determinations. The differences between the pregnant and nonpregnant mice groups shown in this table were analyzed by normal hypothesis test as previously described (Zhou et al., 2008) for the pharmacokinetic data or the Student's t test for the unbound fraction data, and differences with p values <0.05 were considered to be statistically significant.
| Parameter | WT Pregnant | WT Nonpregnant | p Value | Bcrp1(−/−) Pregnant | Bcrp1(−/−) Nonpregnant | p Value |
|---|---|---|---|---|---|---|
| AUCdose-normalized [(μg · min/ml)/μg] | 1.8 ± 0.1 | 3.2 ± 0.1 | <0.01 | 1.7 ± 0.1 | 3.3 ± 0.1 | <0.01 |
| CL (ml/min) | 0.56 ± 0.03 | 0.31 ± 0.01 | <0.01 | 0.60 ± 0.03 | 0.31 ± 0.01 | <0.01 |
| MRT (min) | 63.2 ± 7.7 | 49.5 ± 3.3 | >0.05 | 56.7 ± 4.6 | 51.0 ± 3.9 | >0.05 |
| T1/2 (min) | 43.8 ± 8.8 | 34.3 ± 4.1 | >0.05 | 39.3 ± 6.0 | 35.4 ± 4.7 | >0.05 |
| Vss (ml) | 35.3 ± 4.6 | 15.6 ± 1.2 | <0.05 | 34.2 ± 3.2 | 15.6 ± 1.3 | <0.05 |
| fu (%) | 3.4 ± 0.3 | 3.2 ± 0.3 | >0.05 | 3.9 ± 0.4 | 3.6 ± 0.3 | >0.05 |