Table 1.
DMFa dosage (mg/kg/day) | Mean maternal body weight gain (g, %)b,c | Mean fetal body weight (g, %)c | Fetal skeletal variation: number of bones with ossification | Exposure margine | |
---|---|---|---|---|---|
Hindlimb metatarsalsd | Hindlimb phalangesd | ||||
0 | 89.1 | 5.45 | 4.87 | 6.32 | – |
25 | −1.8 | +1.7 | 4.85 | 6.46 | 1-fold |
100 | −17.3** | +0.9 | 4.83 | 6.36 | 4-fold |
250 | −62.3** | −8.3** | 4.43** | 5.47* | 11-fold |
* P < 0.05 compared to mean control group value
** P < 0.01 compared to mean control group value
aDelayed-release DMF (also known as gastro-resistant DMF); DMF dimethyl fumarate
bBody weight gain during the dosing period gestation days 7–17
cFor controls, group mean is shown. For treated groups, percentage difference from control values are shown. Statistical significance is based on actual data (not on the percent difference)
dMean number of bones with ossification per fetus per litter
eExposure margin ratios calculated based on human area under the curve exposure from United States Package Insert (USPI)