Digoxin transfer across the isolated placenta is influenced by maternal and fetal albumin concentrations

Schmolling, J.; Jung, Sunyo; Reinsberg, Jochen; Schlebusch, H.

doi:10.1071/rd9960969

Cited by 9 publications

(2 citation statements)

References 15 publications

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“…Because only the unbound drug fraction can cross the placenta, the balance between maternal and fetal concentrations of drug‐binding proteins is of particular importance. For example, the placental transfer of digoxin in the perfused cotyledons has been observed to be dependent on the albumin concentrations in both circuits . Also, as discussed later on, the difference in the pH value between the maternal and fetal blood may be another relevant factor influencing the transfer of weakly basic drugs, which should be accounted for in these experiments.…”

Section: Models For Placental Drug Transfermentioning

confidence: 91%

“…For example, the placental transfer of digoxin in the perfused cotyledons has been observed to be dependent on the albumin concentrations in both circuits. 89,90 Also, as discussed later on, the difference in the pH value between the maternal and fetal blood may be another relevant factor influencing the transfer of weakly basic drugs, which should be accounted for in these experiments. Despite these challenges, a recent study of 26 drugs showed that the prediction of ex vivo placenta perfusion matches the observed in vivo data well.…”

Section: Ex Vivo Cotyledon Perfusion Experimentsmentioning

confidence: 98%

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Drug Transporters Expressed in the Human Placenta and Models for Studying Maternal‐Fetal Drug Transfer

Dallmann

Liu

Burckart

et al. 2019

The Journal of Clinical Pharma

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Tremendous efforts have been directed to investigate the ontogeny of drug transporters in fetuses, neonates, infants, and children based on their importance for understanding drug pharmacokinetics. During development (ie, in the fetus and newborn infant), there is special interest in transporters expressed in the placenta that modulate placental drug transfer. Many of these transporters can decrease or increase drug concentrations in the fetus and at birth, stressing the relevance of elucidating expression in the placenta and potential gestational age‐dependent changes therein. Hence, the main objective of this review was to summarize the current knowledge about expression and ontogeny of transporters in the human placenta in healthy pregnant women. In addition, various in vitro, ex vivo, and in silico models that can be used to investigate placental drug transfer, namely, placental cancer cell lines, ex vivo cotyledon perfusion experiments, and physiologically based pharmacokinetic (PBPK) models, are discussed together with their advantages and shortcomings. A particular focus was placed on PBPK models because these models can integrate different types of information, such as expression data, ontogeny information, and observations obtained from the ex vivo cotyledon perfusion experiment. Such a mechanistic modeling framework may leverage the available information and ultimately help to improve knowledge about the adequacy and safety of pharmacotherapy in pregnant women and their fetuses.

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Section: Models For Placental Drug Transfermentioning

confidence: 91%

Section: Ex Vivo Cotyledon Perfusion Experimentsmentioning

confidence: 98%

Drug Transporters Expressed in the Human Placenta and Models for Studying Maternal‐Fetal Drug Transfer

Dallmann

Liu

Burckart

et al. 2019

The Journal of Clinical Pharma

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Transplacental Pharmacokinetics of Flecainide in the Gravid Baboon and Fetus

et al. 2005

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The objective of this study was to characterize the transfer of flecainide across the placenta and determine the fetal: maternal ratio of flecainide in the gravid baboon. Flecainide acetate has been especially successful for the treatment of fetal supraventricular tachycardia associated with hydrops fetalis. However, the degree of transplacental transmission remains unknown. In this study, all animals were placed under general anesthesia. Flecainide 2.5 mg/kg was administered intravenously. Percutaneous umbilical blood sampling was performed simultaneously with maternal sampling. Flecainide levels were measured using high-performance liquid chromatography with ultraviolet detection. A total of six gravid baboons were studied at an average gestational age of 132 days. The mean maternal volume of distribution at steady state was 5.1 +/- 1.8 L/kg. The mean combined elimination constant (k(el)) was 0.79 +/- 0.19 hr(-1) [95% confidence interval (CI), 0.64-0.93]. There was a linear relationship between maternal and fetal concentrations, with a ratio of fetal-to-maternal serum levels of 0.49 +/- 0.05 (95% CI, 0.39-0.59). At steady state, fetal flecainide levels are approximately 50% of maternal flecainide levels. Flecainide is rapidly distributed in the mother and fetus following a single intravenous dose with a maternal volume of distribution similar to that reported in normal healthy human adults. Since fetal levels correlate closely with maternal levels, we propose that it is possible to estimate fetal levels by monitoring maternal levels.

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Photoradiation of perfused placental tissue - a suitable in vitro model for photodynamic therapy?

Schmolling

Brunken

Richter

et al. 2001

Archives of Gynecology and Obstetrics

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Our aim was to evaluate the isolated placental lobule as a model to study the cytotoxic effects of photodynamic therapy (PDT) in vitro. Ten human placental lobules were dually perfused with a modified medium 199 for a 4-hour period. Photosan III was added to the fetal perfusate at a dose of 5 mg/kg tissue, and laser light (630 nm wavelength) provided by an argon-pumped dye laser was applied at 50 J/cm2 in the experimental group (n=5). Potassium and lactate dehydrogenase (LDH) release into the perfusate as well as the transplacental creatinine passage from PDT-treated placentas and control placentas (n=5) were compared, and light microscopic examinations of the placental tissue were performed after the experiments. Potassium release into the fetal perfusate was higher in the PDT-treated placental lobules (p<0.05), and weight gain during the artificial perfusion suggests the development of edema only in the photoradiated lobules (p<0.01). The release of the bigger molecules of the LDH however was comparable in the two experimental groups, and transplacental creatinine passage was not affected by photoradiation. Light microscopic examinations demonstrated lesions at the cytotrophoblast, the syncytiotrophoblast and the endothelium of the fetal vessels of the photoradiated placentas, although they were not specific and could also be found in the control tissue. We conclude that the isolated placenta may be used to study cytotoxic effects of photoradiation in vitro, but better specifity and sensitivity might be achieved if a. The perfusion time is prolonged to make the difference between the experimental and the control group clearer and b. Electron microscopic investigations are made to demonstrate intracellular lesions of the mitochondria and the endoplasmic reticulum.

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Digoxin transfer across the isolated placenta is influenced by maternal and fetal albumin concentrations

Cited by 9 publications

References 15 publications

Drug Transporters Expressed in the Human Placenta and Models for Studying Maternal‐Fetal Drug Transfer

Drug Transporters Expressed in the Human Placenta and Models for Studying Maternal‐Fetal Drug Transfer

Transplacental Pharmacokinetics of Flecainide in the Gravid Baboon and Fetus

Photoradiation of perfused placental tissue - a suitable in vitro model for photodynamic therapy?

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