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.

High dose of antacid (Mylanta II) reduces bioavailability of ranitidine.

To investigate the effect of antacid on the bioavailability and disposition of ranitidine six healthy volunteers were studied on two occasions one week apart. In the first study the received ranitidine 150 mg with 60 ml water, and in the second study they received ranitidine 150 mg plus 30 ml of an aluminium/magnesium hydroxide mixture (Mylanta II) and 30 ml water. Giving antacid reduced both the maximum plasma ranitidine concentration and the area under the curve by one-third; elimination of the drug was not changed. Thus giving a high dose of antacid significantly diminished the bioavailability of ranitidine.