The transfer and metabolism of corticosteroids in the perfused human placenta

Levitz, Mortimer; Jansen, Valerie; Dancis, Joseph

doi:10.1016/0002-9378(78)90768-8

Cited by 102 publications

(25 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a result of 11␤-HSD type 2 enzyme activity in placental syncytiotrophoblast (73), there is a great difference in transplacental passage between cortisol and prednisolone on the one hand, and betamethasone and dexamethasone on the other hand (74). In contrast to dexamethasone and betamethasone, prednisolone and methylprednisolone are extensively inactivated in placental tissue (12,75,76).…”

Section: Transplacental Passage Of Synthetic Corticosteroidsmentioning

confidence: 97%

Corticosteroids, Pregnancy, and HELLP Syndrome: A Review

Heimel¹,

Franx²,

Schobben³

et al. 2005

Obstetrical & Gynecological Survey

View full text Add to dashboard Cite

Corticosteroids are potent antiinflammatory and immunosuppressive drugs, which are used in the treatment of a wide range of medical disorders. During pregnancy, several corticosteroids are administered for maternal as well as fetal reasons. Prednisone and prednisolone show limited transplacental passage and are thus used for treatment of maternal disease. Dexamethasone and betamethasone, drugs that can easily cross the placenta, are more suitable for fetal indications. During the last decade, administration of corticosteroids was introduced in the treatment of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome), a severe form of preeclampsia unique to human pregnancy. Several randomized, controlled trials as well as other prospective and retrospective studies have been performed to investigate this beneficial effect of corticosteroids on biochemical measures and clinical signs. This review discusses the characteristics of corticosteroids in humans and details the use of corticosteroids during pregnancy. A review of literature on the effect of corticosteroids on HELLP syndrome is given and possible mechanisms of action are discussed.

show abstract

Section: Transplacental Passage Of Synthetic Corticosteroidsmentioning

confidence: 97%

Corticosteroids, Pregnancy, and HELLP Syndrome: A Review

Heimel¹,

Franx²,

Schobben³

et al. 2005

Obstetrical & Gynecological Survey

View full text Add to dashboard Cite

show abstract

“…In vitro metabolism studies of synthetic corticosteroids with human and rat placenta have shown that fluorinated corticosteroids such as dexamethasone and betamethasone exhibit minimal placental metabolism (19,23). Greater metabolism of fluorinated corticosteroids has been reported using the perfused human placenta preparation (24). However, the results from the perfused placenta experiments are difficult to rely upon because these experiments were performed with low albumin concentrations in the perfusion medium, which does not resemble the in vivo situation.…”

Section: Introductionmentioning

confidence: 97%

Area/Moment and Compartmental Modeling of Pharmacokinetics During Pregnancy: Applications to Maternal/Fetal Exposures to Corticosteroids in Sheep and Rats

Samtani

Schwab

Nathanielsz³

et al. 2004

Pharm Res

View full text Add to dashboard Cite

show abstract

“…Thus, greater metabolism of betamethasone has been shown in the perfused human placenta. 29 A study in pregnant sheep has also shown that placental transfer of dexamethasone is limited. 30 Another poorly understood process that could possibly explain the limited placental transfer of dexamethasone and betamethasone is the removal of these steroids by placental transporters that protect the fetus by removing toxic endogenous compounds and xenobiotics from the developing conceptus.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of Betamethasone and Fetal Cardiovascular Adverse Effects in Pregnant Sheep After Different Doses

Schwab

Coksaygan

Samtani

et al. 2006

Obstetrics & Gynecology

View full text Add to dashboard Cite

OBJECTIVE-To study the pharmacokinetics of different betamethasone doses and preparations used to enhance fetal lung maturation in the maternal and fetal circulation of sheep and the adverse effects on fetal blood pressure.METHODS-Doses of 170 (n = 6) and 110 µg/kg (n = 6) betamethasone phosphate equivalent to 12 or 8mg, respectively, administered to a 70kg pregnant woman or 170 µg/kg (n = 6) of a depot formulation (50% betamethasone phosphate and 50% betamethasone acetate) were injected intramuscularly to chronically instrumented pregnant sheep.RESULTS-Both betamethasone preparations produced highest maternal concentrations after 15 min followed by an exponential decline with a t 1/2 of about 3 hours. The drug fell below the limit of detection at 8 to 12 hours. Betamethasone was first detectable in the fetal circulation at 1 hour, peaked at 3 hours, and decreased below the limit of detection at 8 hours independently of the dose or preparation. Maternal and fetal betamethasone concentrations achieved with the phosphate and acetate formulation were one half of those obtained with betamethasone phosphate, suggesting that very little betamethasone is released from the acetate within the first 8 hours when the effect on lung maturation is needed. Betamethasone led to a maximal increase of mean fetal blood pressure from 42 ± 1 to 51 ± 1 mm Hg (P<.05) and did not differ between the doses and preparations, although plasma concentrations showed a clear dose-concentration relationship.CONCLUSION-The doses of betamethasone used in obstetrics are supramaximal in terms of cardiovascular effects in sheep. Risk-benefit studies are needed to find the effective steroid dose with the least adverse effects.Administration of synthetic glucocorticoids to women in premature labor has a clearly proven clinical benefit in decreasing the incidence of respiratory distress syndrome and Although it has been shown in sheep that repeated treatments may be of benefit for the lung, 12 to our knowledge there has never been a study designed to examine a broad range of doses at the clinical level to determine the dose of maternal glucocorticoid that is optimal for the effects on the fetus in rodents, sheep, nonhuman primates or humans (PubMed, January 1966-January 2006; no language restrictions; search terms: antenatal or prenatal; glucocorticoids, steroids or betamethasone; dose or pharmacokinetics; lung or blood pressure). Recommendations 1 for dose and timing of treatments are mainly based on the study of Liggins and Howie 13 who chose the dose for clinical trials partly from the doses used in experiments with sheep. Retrospective data collected on mothers who received only a partial course of steroids, however, suggests that any exposure to an appropriate corticosteroid has beneficial effects on postnatal outcome. 14 The present study was designed to estimate the time course of maternal and fetal betamethasone concentrations after maternal exposure to two doses and two different betamethasone preparations frequently used clinically i...

show abstract

The transfer and metabolism of corticosteroids in the perfused human placenta

Cited by 102 publications

References 9 publications

Corticosteroids, Pregnancy, and HELLP Syndrome: A Review

Corticosteroids, Pregnancy, and HELLP Syndrome: A Review

Area/Moment and Compartmental Modeling of Pharmacokinetics During Pregnancy: Applications to Maternal/Fetal Exposures to Corticosteroids in Sheep and Rats

Kinetics of Betamethasone and Fetal Cardiovascular Adverse Effects in Pregnant Sheep After Different Doses

Contact Info

Product

Resources

About