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

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.

Decreased placental and transcellular permeation of cefuroxime in pregnant women with diabetes.

BACKGROUND: The present study investigated the transcellular and placental permeation of cefuroxime, an antibiotic used in cesarean sections, in pregnant women with diabetes and hypertension. METHODS: Fifty-three women scheduled for cesarean section were divided into three groups: healthy women (n = 18), women with arterial hypertension (n = 21), and women with gestational diabetes (n = 14). All women received 1.5 g, i.v., cefuroxime. Cefuroxime concentrations were measured in maternal venous plasma before, during, and after delivery, as well as in fetal umbilical cord vein and artery plasma during delivery. The effects of diabetes and hypertension on cefuroxime placental-permeation were assessed by the fetomaternal plasma concentration ratios. Pharmacokinetic non-compartmental model analyses were performed and results were compared using anova. RESULTS: Fetomaternal drug concentration ratios were lower in the diabetic group than in the hypertensive and control groups. There were no significant differences in umbilical arterial : venous plasma drug concentration ratios in the diabetic and hypertensive groups compared with the control group. Apparent volume of distribution and clearance were significantly lower in the diabetic group compared with the control and hypertensive groups. CONCLUSIONS: Diabetes led to decreased placental transfer of cefuroxime, as well as volume of distribution and clearance, but did not affect other pharmacokinetic parameters. Hypertension had no significant effect on the permeation of cefuroxime or on its pharmacokinetics. Prophylactic concentrations of cefuroxime were reached in all groups, but the dosing time of cefuroxime should not be less than 30 min or greater than 2 h prior to delivery.

Diabetes and hypertension increase the placental and transcellular permeation of the lipophilic drug diazepam in pregnant women.

BACKGROUND: Previous studies carried out in our laboratories have demonstrated impaired drug permeation in diabetic animals. In this study the permeation of diazepam (after a single dose of 5 mg/day, administered intramuscularly) will be investigated in diabetic and hypertensive pregnant women. METHODS: A total 75 pregnant women were divided into three groups: group 1 (healthy control, n = 31), group 2 (diabetic, n = 14) and group 3 (hypertensive, n = 30). Two sets of diazepam plasma concentrations were collected and measured (after the administration of the same dose of diazepam), before, during and after delivery. The first set of blood samples was taken from the mother (maternal venous plasma). The second set of samples was taken from the fetus (fetal umbilical venous and arterial plasma). In order to assess the effect of diabetes and hypertension on diazepam placental-permeation, the ratios of fetal to maternal blood concentrations were determined. Differences were considered statistically significant if p ≤ 0.05. RESULTS: The diabetes and hypertension groups have 2-fold increase in the fetal umbilical-venous concentrations, compared to the maternal venous concentrations. Feto: maternal plasma-concentrations ratios were higher in diabetes (2.01 ± 1.10) and hypertension (2.26 ± 1.23) groups compared with control (1.30 ± 0.48) while, there was no difference in ratios between the diabetes and hypertension groups. Umbilical-cord arterial: venous ratios (within each group) were similar among all groups (control: 0.97 ± 0.32; hypertension: 1.08 ± 0.60 and diabetes: 1.02 ± 0.77). CONCLUSIONS: On line with our previous findings which demonstrate disturbed transcellular trafficking of lipophilic drugs in diabetes, this study shows significant increase in diazepam placental-permeation in diabetic and hypertensive pregnant women suggesting poor transcellular control of drug permeation and flux, and bigger exposure of the fetus to drug-placental transport.

[Significance of serum ferritin level in the prediction of delivery of low birth weight newborns for gestational age].

INTRODUCTION: Intrauterine growth restriction is one of the leading causes of prenatal morbidity and mortality. As there is no causal therapy, prediction of intrauterine growth retardation is one of the priorities of prenatal healthcare. OBJECTIVE: The purpose of this study was to analyze blood ferritin level, and erythrocyte, hemoglobin and hematocrit count in pregnant women between 30-32 weeks of gestation and to set apart those with a possible development of intrauterine growth restriction. METHODS: A prospective study was conducted that included 220 healthy pregnant women between 30-32 gestational weeks. The study was done at the Clinical Center of Vojvodina, Department of Obstetrics and Gynecology Novi Sad and Clinical laboratory from March 1, 2008 to November 30, 2009. Serum ferritin level, hemoglobin, hematocrit and erythrocyte count were determined from blood samples of all pregnant women. RESULTS: After term delivery, 8.1% of pregnant women gave birth to low birth weight babies for gestational age but without anemia.The value of ferritin, hemoglobin, hematocritanderythrocyte was significantly higher in women with low birth weight babies. In mothers with low birth weight newborns serum ferritin level was on the average for 6.4 g/l higher than in mothers with normal weight newborns (p<0.005). Statistically, ROC curve analysis showed that the pregnant women with the ferritin level above 13.6 microg/L, and with erythrocyte count >3.76x10(12)/L, hemoglobin >117 g/L and hematocrit >32.9%, in the period of 30-32 weeks of gestation, also had a significantly higher probability of having a low birth weight newborn for gestational age (p<0.05). CONCLUSION: Based on the level of ferritin and other parameters in the period of 30-32 weeks of gestation, we can predict pregnant women in whom we can expect development of intrauterine growth restriction.