Table 1. Summary of Experimental Data from Pregnant Mice used in the PBPK Modela.
| Oral | IV | ||
|---|---|---|---|
| Sample sizeb | Measured time (h) | Measured time (h) | Purpose |
| Plasma (n = 4–6)c | 2, 4, 8, 12, 24, 36, 48, 72, 96 | 0.5, 2, 4, 8, 12, 24, 48, 72, 96 | Calibration |
| Liver (n = 2–4)d | 2, 4, 8, 12, 24, 48, 96 | 2, 4, 8, 12, 24, 48, 96 | Calibration |
| Fetal brain (n = 2–4)d | 2, 4, 8, 12, 24, 48, 96 | 2, 4, 8, 12, 24, 48, 96 | Calibration |
| Fetal liver (n = 2–4)d | 2, 4, 8, 12, 24, 48, 96 | 2, 4, 8, 12, 24, 48, 96 | Evaluation |
| Placenta (n = 2–4)d | 2, 4, 8, 12, 24, 48, 96 | 2, 4, 8, 12, 24, 48, 96 | TK study |
| Amniotic fluid (n = 4) | 96 | 96 | Evaluation |
| Fat (n = 4) | 96 | 96 | Evaluation |
| Brain (n = 4)e | 96 | 96 | Evaluation |
| Heart (n = 4)e | 96 | 96 | Evaluation |
| Spleen (n = 4)e | 96 | 96 | Evaluation |
| Kidney (n = 4) | 96 | 96 | TK study |
| Small intestine (n = 4) | 96 | 96 | TK study |
| Stomach (n = 4) | 96 | 96 | TK study |
| Urine (n = 4)f | 0, 0–2, 2–4, 4–8, 8–12, 12–24, 24–36, 36–48, 48–72, 72–96 | 0, 0–2, 2–4, 4–8, 8–12, 12–24, 24–36, 36–48, 48–72, 72–96 | TK study |
| Feces (n = 4)f | 0, 0–2, 2–4, 4–8, 8–12, 12–24, 24–36, 36–48, 48–72, 72–96 | 0, 0–2, 2–4, 4–8, 8–12, 12–24, 24–36, 36–48, 48–72, 72–96 | TK study |
a
PBPK, physiologically based pharmacokinetic. Measured time refers to the time after exposure, i.e., 0 h refers to the beginning of GD13; “TK study” refers to data only used to calculate the accumulation.
b
For each time point.
c
Obtained plasma from the repeat blood collection group (n = 4) at each time point and additionally obtained plasma from euthanasia group (n = 2) at time points of 2, 4, 8, 12, 24, and 48 h.
d
At 96 h, four were euthanized and at the remaining time points, two were euthanized.
e
The mean value of the concentrations in these three tissues was taken as the concentration of the rest of the body.
f
Collected from the repeat blood collection group.