A comparison of the bioavailability of oral and intramuscular dexamethasone in women in late pregnancy

Egerman, Robert; Pierce, William F.; Andersen, Richard N.; Umstot, Edward S.; Carr, Teresa; Sibai, Bahaeddine M

doi:10.1016/s0029-7844(96)00446-2

Cited by 36 publications

(20 citation statements)

References 10 publications

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“…( e ) Simulated (lines; 10 × 11 virtual individuals) and observed (data points; from ref. ) mean plasma concentration‐time profiles of dexamethasone after a single oral dose of 8 mg (blue line, filled circles) or a single i.m. dose of 6 mg (solid black line, open circles) in pregnant subjects (mean gestational age: 30 weeks).…”

Section: Resultsmentioning

confidence: 98%

Evaluation of Maternal Drug Exposure Following the Administration of Antenatal Corticosteroids During Late Pregnancy Using Physiologically‐Based Pharmacokinetic Modeling

Milad²

2019

Clin Pharma and Therapeutics

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Betamethasone and dexamethasone are the most widely studied antenatal corticosteroids (ACS) administered to pregnant women, just prior to the birth of a preterm neonate, to accelerate fetal lung maturation. Although betamethasone, predominantly used in developed countries, has been shown to be an effective and safe intervention for reducing neonatal mortality, the choice of ACS and optimal dosing in low and middle income countries (LMICs) remains unclear. This is primarily because the exposure-response relationships have not been established for ACS despite the long history of use. As the first step toward the optimal use of ACS in LMICs, we developed physiologically-based pharmacokinetic (PBPK) models to describe the kinetics of ACS following i.v., p.o., or i.m. dosing. In vitro data describing the cytochrome P450 3A4 enzyme contribution were incorporated and this was refined using clinical data. The models can be applied prospectively to predict kinetics of ACS in pregnant women receiving various dosing regimens.Preterm birth is a major cause of death and morbidity in newborns worldwide and the majority of preterm deliveries and deaths occur in sub-Saharan African and South Asian countries. 1 Respiratory morbidity, including respiratory distress syndrome (RDS), is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. The administration of antenatal corticosteroids (ACS) to a pregnant woman (who is at risk of imminent preterm birth) is recommended to promote fetal

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Section: Resultsmentioning

confidence: 98%

Evaluation of Maternal Drug Exposure Following the Administration of Antenatal Corticosteroids During Late Pregnancy Using Physiologically‐Based Pharmacokinetic Modeling

Milad²

2019

Clin Pharma and Therapeutics

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“…In contrast, two reports indicate T max at about 2 hours for oral Dex and 1 hour for i.m. Dex in pregnant women . However, Queckenberg et al .…”

Section: Discussionmentioning

confidence: 96%

“…Dex in pregnant women. 19,20 However, Queckenberg et al 21 reported maximal peak concentrations at 1 hour for oral Dex in fasted adults. Another variable confounding virtually all previous clinical PK studies is that at early times plasma will contain the prodrugs, BetaP or DexP.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Intramuscular and Oral Betamethasone and Dexamethasone in Reproductive Age Women in India

Jobe

Milad²,

Peppard

et al. 2019

Clinical Translational Sci

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High‐dose betamethasone and dexamethasone are standard of care treatments for women at risk of preterm delivery to improve neonatal respiratory and mortality outcomes. The dose in current use has never been evaluated to minimize exposures while assuring efficacy. We report the pharmacokinetics and pharmacodynamics (PDs) of oral and intramuscular treatments with single 6 mg doses of dexamethasone phosphate, betamethasone phosphate, or a 1:1 mixture of betamethasone phosphate and betamethasone acetate in reproductive age South Asian women. Intramuscular or oral betamethasone has a terminal half‐life of 11 hours, about twice as long as the 5.5 hours for oral and intramuscular dexamethasone. The 1:1 mixture of betamethasone phosphate and betamethasone acetate shows an immediate release of betamethasone followed by a slow release where plasma betamethasone can be measured out to 14 days after the single dose administration, likely from a depo formed at the injection site by the acetate. PD responses were: increased glucose, suppressed cortisol, increased neutrophils, and suppressed basophils, CD3CD4 and CD3CD8 lymphocytes. PD responses were comparable for betamethasone and dexamethasone, but with longer times to return to baseline for betamethasone. The 1:1 mixture of betamethasone phosphate and betamethasone acetate caused much longer adrenal suppression because of the slow release. These results will guide the development of better treatment strategies to minimize fetal and maternal drug exposures for women at risk of preterm delivery.

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“…It is administered during pregnancy to normalize lung morphology inducing structural and functional maturity in preterm human infants with bronchopulmonary dysplasia and so decreasing mortality [4]. Fetal exposure to an excess of glucocorticoids has been implicated as a causative factor in fetal growth restriction called intrauterine growth retardation (IUGR) [5].…”

Section: Introductionmentioning

confidence: 99%

“…Fetal exposure to an excess of glucocorticoids has been implicated as a causative factor in fetal growth restriction called intrauterine growth retardation (IUGR) [5]. The effects of prenatal Dex therapy on the fetal skeletal system need to be clarified because this kind of therapy can result in more disadvantages than advantages, especially in the long-term consequences in postnatal life and adulthood [1,[4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Effect of maternal dexamethasone and alpha-ketoglutarate administration on skeletal development during the last three weeks of prenatal life in pigs

Sliwa¹,

Tatara²,

Nowakowski³

et al. 2006

The Journal of Maternal-Fetal & Neonatal Medicine

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A comparison of the bioavailability of oral and intramuscular dexamethasone in women in late pregnancy

Abstract: The bioavailability of 8 mg of oral dexamethasone is similar to that of a 6-mg IM dose, as determined by the area under the curve.

Cited by 36 publications

References 10 publications

Evaluation of Maternal Drug Exposure Following the Administration of Antenatal Corticosteroids During Late Pregnancy Using Physiologically‐Based Pharmacokinetic Modeling

Evaluation of Maternal Drug Exposure Following the Administration of Antenatal Corticosteroids During Late Pregnancy Using Physiologically‐Based Pharmacokinetic Modeling

Pharmacokinetics and Pharmacodynamics of Intramuscular and Oral Betamethasone and Dexamethasone in Reproductive Age Women in India

Effect of maternal dexamethasone and alpha-ketoglutarate administration on skeletal development during the last three weeks of prenatal life in pigs

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