The Effect of Diabetes and Hypertension on the Placental Permeation of the Hydrophilic Drug, Ranitidine

Abstract

Introduction Ranitidine is a hydrophilic weak base and an H2-receptor antagonist which is commonly used for gastroesophageal reflux, including during pregnancy. It has limited placental permeation and can be used as a pre-anesthetic antacid to prevent aspiration of acidic stomach contents. Recent studies suggest that diabetes and hypertension may influence placental permeation of hydrophilic drugs. Thus, this study aimed to investigate the influence of diabetes and hypertension on ranitidine's placental permeation in pregnant women. Methods Forty one pregnant women all scheduled for elective cesarean section entered the study: healthy control (n = 15), with hypertension (n = 16) and with gestational diabetes (n = 10). All women received 50 mg of ranitidine intravenously. Three samples of maternal plasma (after ranitidine application, at delivery and after delivery), and two umbilical cord samples (arterial and venous blood) were collected and analyzed for ranitidine concentrations. Maternal pharmacokinetic parameter were calculated as well as feto:maternal and umbilical cord arterial to venous concentration ratios. Results Ranitidine maternal and umbilical cord (arterial and venous) concentrations were similar in all three groups and there were no difference between feto:maternal ratios nor volume of distribution, clearance and half life between the groups. Discussion Fetal concentrations are dependent on maternal concentrations in healthy and hypertensive women but not in diabetic women. Hypertension and diabetes did not affect fetal handling of ranitidine. Though hypertension and diabetes did not influence ranitidine placental permeation, it appears they altered time needed to achieve unity between maternal and fetal plasma.