Dataset Information

Transplacental transfer and distribution of pravastatin.

ABSTRACT:

Objective

The objective of the study was to determine the bidirectional transfer of pravastatin across the dually perfused term human placental lobule and its distribution between the tissue and maternal and fetal circuits.

Study design

The transfer of pravastatin was determined in the maternal-to-fetal (n = 11) and fetal-to-maternal (n = 10) directions. Pravastatin was coperfused with its [(3)H]-isotope and the marker compound antipyrine (20 ?g/mL) and its [(14)C]-isotope. The concentration of pravastatin in the perfused tissue and the maternal and fetal circuits was determined using liquid scintillation spectrometry. Inside-out vesicles prepared from placental brush border membranes were utilized to investigate the role of efflux transporters in the transplacental transfer of pravastatin.

Results

Pravastatin was transferred from the maternal to the fetal circuit and vice versa. In the maternal-to-fetal direction, the distribution of pravastatin at the end of experiment was as follows: 14 ± 5% of the drug was retained by the tissue, 68 ± 5% remained in the maternal circuit, and 18 ± 4% was transferred to the fetal circuit. The normalized transfer of pravastatin (clearance index) to antipyrine in the fetal-to-maternal direction (0.48 ± 0.07) was higher than its transfer in the maternal-to-fetal direction (0.36 ± 0.07, P < .01). Furthermore, pravastatin inhibited the adenosine triphosphate (ATP)-dependent uptake of the paclitaxel and estrone sulfate.

Conclusion

The transfer of pravastatin across the dually perfused placental lobule suggests that fetal exposure to pravastatin is plausible. The higher transfer of pravastatin in the fetal-to-maternal direction than the reverse as well as its inhibition of the ATP-dependent uptake of [(3)H]-paclitaxel and [(3)H]-estrone sulfate strongly suggest the involvement of efflux transporters in decreasing its transfer across the placenta and support pravastatin's favorable pharmacokinetic profile in pregnancy.

SUBMITTER: Nanovskaya TN

PROVIDER: S-EPMC3891837 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Publications

Transplacental transfer and distribution of pravastatin.

Nanovskaya Tatiana N TN Patrikeeva Svetlana L SL Paul Jonathan J Costantine Maged M MM Hankins Gary D V GD Ahmed Mahmoud S MS

American journal of obstetrics and gynecology 20131001 4

<h4>Objective</h4>The objective of the study was to determine the bidirectional transfer of pravastatin across the dually perfused term human placental lobule and its distribution between the tissue and maternal and fetal circuits.<h4>Study design</h4>The transfer of pravastatin was determined in the maternal-to-fetal (n = 11) and fetal-to-maternal (n = 10) directions. Pravastatin was coperfused with its [(3)H]-isotope and the marker compound antipyrine (20 μg/mL) and its [(14)C]-isotope. The co ...[more]

PMID: 24070396

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Project description:Transplacental antibody transfer from mother to fetus provides protection from infection in the first weeks of life, and the four different subclasses of IgG (IgG1, IgG2, IgG3, and IgG4) have diverse roles in protection against infection. In this study, we evaluated concentrations and transplacental transfer ratios of the IgG subclasses in a healthy UK-based cohort of mother-cord pairs, and investigated associations with maternal, obstetric, and fetal factors. In agreement with previous studies, we found a strong association between maternal and cord IgG for all subclasses. We report a transfer efficiency hierarchy of IgG1>IgG3>IgG4=IgG2 in our study population, and our review of the literature demonstrates that there is no consensus in the hierarchy of subclass transfer, despite the commonly made statement that the order is IgG1>IgG4>IgG3>IgG2. We report additional data regarding negative associations between elevated maternal IgG concentrations and maternal/cord transfer ratios, finding an effect on IgG1, IgG2, and IgG3 subclasses. Levels of IgG subclasses were the same between venous and arterial blood samples from the umbilical cord, but there was a significantly higher level of total IgG in arterial blood. We found no correlation between placental FcRn protein levels and IgG transfer in our cohort, suggesting that IgG is the main determinant of observed differences in transplacental transfer ratios at term. Neonatal IgG1 and IgG4 levels were increased with later gestation at delivery, independent of any increase in transplacental transfer, indicating that the benefit of later gestation is through accumulation of these subclasses in the fetus. Neonatal IgG2 levels and transfer ratios were reduced in rhesus-negative pregnancies, suggesting that administered anti-D antibodies may compete for transplacental transfer of this subclass. Maternal influenza vaccination resulted in elevated maternal and neonatal levels of IgG4, whereas maternal Tdap vaccination had no impact on neonatal levels of the subclasses, nor transfer. However, within Tdap vaccinated pregnancies, later gestation at Tdap vaccination was associated with higher transplacental transfer. Our study provides information regarding levels and transfer of IgG subclasses in healthy term pregnancies and demonstrates the importance of recording detailed clinical information in studies of antibody transfer, including parity, ethnicity, and timing of maternal vaccine delivery.

Project description:BackgroundPer- and polyfluoroalkyl substances (PFASs) are a growing public health concern. Some longer chain PFASs bioaccumulate and many compounds persist in the environment for long time periods. Recent studies have established their ability to pass through placenta, yet data on the transplacental transfer efficiency and partitioning of short and long chain PFASs in blood matrices are limited.ObjectivesTo assess predictors of the partitioning of 17 PFAS compounds detected in the maternal serum, umbilical cord serum and whole cord blood samples from matched mother-newborn pairs from two Faroe Islands cohorts.MethodsWe examined 151 mother-newborn pairs from two successive Faroese birth cohorts. Cord:maternal serum (transplacental transfer) and serum:whole cord blood (blood partitioning) ratios were estimated for 17 PFAS compounds. We also examined the relationships of these ratios with maternal, newborns', and physico-chemical properties using multivariable regression analyses.ResultsModerate to high correlations were observed between maternal and cord serum PFAS concentrations (ρ: 0.41 to 0.95), indicating significant transfer of these compounds from the mother to the fetus. Median transplacental transfer ratios were generally below 1, except for perfluorooctane sulfonamide (FOSA), and ranged between 0.36 for perfluorodecanoate (PFDA) and perfluoroundecanoate (PFUnDA) and 1.21 for FOSA. Most PFASs exhibited a preference to the serum component of the blood, except FOSA and perfluoroheptanoate (PFHpA), with blood partitioning ratios ranging from 0.36 for FOSA to 2.75 for PFUnDA. Both the functional groups and carbon chain length of different PFASs were important predictors of transplacental transfer and blood partitioning. We observed a U-shaped relationship between transplacental transfer ratios and carbon chain length for perfluorocarboxylates and perfluorosulfonates. Importantly, gestational diabetes was also a strong predictor of transplacental transfer ratios, with significantly higher transfer in mothers with gestational diabetes.ConclusionsOur findings provide a better understanding of the transplacental transfer and blood partitioning of a large number of PFAS compounds. Results elucidate the importance of chemical structure for future risk assessments and choice of appropriate blood matrices for measurement of PFAS compounds.

Dataset Information

Transplacental transfer and distribution of pravastatin.

Objective

Study design

Results

Conclusion

Publications

Transplacental transfer and distribution of pravastatin.

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