The placental transfer of betamethasone

Petersen, M. C.; Nation, Roger L.; Ashley, John J.; McBride, W. G.

doi:10.1007/bf00563006

Cited by 53 publications

(38 citation statements)

References 8 publications

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“…On the other side, potential adverse effects are concealed in the same systems, especially in the cardiovascular [7][8][9][10][11] and central nervous system. [2][3][4][5][6] In conclusion, our study extends findings from previous investigations of the pharmacokinetics of clinical doses of betamethasone phosphate acetate 34 and dexamethasone phosphate 8 in pregnant sheep. The pregnant sheep seems to be an adequate model for pharmacokinetics of betamethasone in human pregnancy.…”

Section: Discussionsupporting

confidence: 88%

“…Placental transfer of betamethasone in humans has been demonstrated, and concentration ratios of maternal venous and fetal cord plasma averaged 0.37 26 or 0.40 33 after maternal intramuscular injection of 12 mg betamethasone phosphate acetate and 0.28 after maternal intramuscular injection of 8 mg betamethasone phosphate. 34 Because cord plasma samples were taken during delivery, sample times varied between 1.5 and 78 hours, 1 and 61, and 2 and 7 hours after treatment, and gestational ages ranged between 25 and 32, 27 and 34, and 31 and 38 weeks, respectively. Generally, these values are comparable to those that we observed in sheep.…”

Section: Discussionmentioning

confidence: 99%

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

Schwab

Coksaygan

Samtani

et al. 2006

Obstetrics & Gynecology

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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...

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Section: Discussionsupporting

confidence: 88%

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

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“…The plasma concentrations of dexamethasone measured in fetal sheep were similar to values measured in human umbilical cord blood within 24 h of a course of antenatal glucocorticoid therapy (13,14). Although maternal injection with dexamethasone would have exposed the ewe and the fetus to initially high then rapidly decreasing concentrations of synthetic glucocorticoid, the plasma concentrations in maternal and fetal blood at the onset of H1 were similar to those reported previously 8 h after injection in the pregnant ewe and the fetus (15) and to those reported in the fetus after 24 h of direct i.v.…”

Section: Discussionsupporting

confidence: 63%

Pituitary-Adrenal Responses to Acute Hypoxemia During and After Maternal Dexamethasone Treatment in Sheep

et al. 2004

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The effects of maternal dexamethasone treatment on hypothalamic-pituitary-adrenal axis function were determined during basal and hypoxemic conditions in maternal and fetal sheep. Under halothane, ewes and their fetuses were catheterized at 117 d gestation (term ϭ 145 d). Starting at 124 d, the ewes received i.m. injections of two doses of either dexamethasone (12 mg) or saline at 24-h intervals. All animals experienced one episode of hypoxemia when the dexamethasone was present in the maternal and fetal circulations [125 Ϯ 1 d (H1)] and a second episode of hypoxemia when the steroid was no longer detectable in either the maternal or fetal circulations [128 Ϯ 1 d (H2)]. The fall in partial pressure of oxygen in arterial blood in response to hypoxia was similar in the two episodes in both the fetal and the maternal blood. Maternal dexamethasone treatment diminished maternal and fetal basal plasma cortisol but not ACTH during the normoxic period of H1 but not H2. In control animals, hypoxemia induced increases in fetal but not maternal ACTH and cortisol concentrations. In dexamethasone-treated animals, maternal ACTH and cortisol concentrations also remained unchanged from baseline in both H1 and H2. In contrast, fetal plasma ACTH and cortisol responses to hypoxemia were significantly suppressed during H1 but not H2. Correlation of fetal plasma ACTH and cortisol concentrations suggested diminished cortisol output without a change in adrenocortical responsiveness in dexamethasone-treated fetuses during H1 but not H2. Since the pioneering discovery of Liggins (1) that glucocorticoids are essential for the maturation of fetal systems in preparation for extrauterine life, synthetic glucocorticoids, such as dexamethasone, have been used routinely in human clinical practice to treat pregnant women who are at risk of preterm delivery (2-4). Such prophylactic treatment mimics the normal prepartum increase in endogenous cortisol output by the fetal adrenal that switches tissue accretion to differentiation (5). Antenatal glucocorticoid treatment has resulted in significant decreases in the incidence of respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, and neonatal mortality associated with preterm birth (3,6).Despite the clear benefits of antenatal glucocorticoid therapy, concerns have been expressed about the safety of the current dosing regimen, in particular with regards to maternal and fetal adrenal suppression resulting from negative feedback by the synthetic steroid (4). In addition, the effects of synthetic glucocorticoids on the fetal defense responses to hypoxemic insults have been identified by the National Institutes of Health in the United States as an area of research needed to guide intrapartum clinical care (4). This is important for two reasons. First, the ovine hypothalamic-pituitary-adrenal (HPA) axis is activated in response to acute hypoxemia in the mother and the fetus and plays an integral role in the fetal defense response to acute hypoxemia (7). Second, episodes of ...

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“…We previously reported the placental transfer of BET (Petersen et al, 1980b) and its disposition after i.v. administration to non-pregnant (Petersen et al, 1983b) and pregnant (Petersen et al, 1983a) (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Disposition of betamethasone in parturient women after intramuscular administration.

Petersen¹,

Ashley

McBride³

et al. 1984

Brit J Clinical Pharma

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The placental transfer of betamethasone

Cited by 53 publications

References 8 publications

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

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

Pituitary-Adrenal Responses to Acute Hypoxemia During and After Maternal Dexamethasone Treatment in Sheep

Disposition of betamethasone in parturient women after intramuscular administration.

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