Placental transfer of omeprazole in maternal and fetal sheep

The placental transfer of omeprazole was studied over a 4-fold dose range in 7 nonanesthetized near-term pregnant sheep. There was a 5 to 1 maternal to fetal transplacental gradient of steady-state total omeprazole concentrations after both low dose (maternal plasma 556 +/- 361 ng/ml, fetal plasma 101 +/- 57 ng/ml) and high dose (maternal plasma 2,660 +/- 1,130 ng/ml, fetal plasma 563 +/- 182 ng/ml). Although this was in part due to differences in plasma protein binding between mother (unbound fraction 6.6 +/- 5.5%) and fetus (unbound fraction 11.9 +/- 2.4%), a 2 to 1 maternal to fetal gradient of steady-state unbound omeprazole concentration was still present (144 +/- 73 ng/ml vs. 64 +/- 32 ng/ml). Fetal omeprazole total plasma concentrations correlated strongly with maternal total drug concentrations (r = 0.84, p less than 0.025) and with the inverse of maternal omeprazole total systemic clearance (r = 0.77, p less than 0.05), indicating that maternal drug disposition was a major determinant of fetal omeprazole plasma concentrations. Urinary clearance of omeprazole was low in both mother (0.137 +/- 0.046 ml/min) and fetus (0.067 +/- 0.039 ml/min). This study demonstrates that the fetus is exposed to about one half of the unbound omeprazole concentration in maternal plasma and suggests that the extent of fetal exposure is largely dictated by maternal drug distribution and elimination characteristics.