Oral antenatal corticosteroids evaluated in fetal sheep

Augusto F. Schmidt, Alan H. Jobe, Paranthaman S. Kannan, James P. Bridges, John P. Newnham, Masatoshi Saito, Haruo Usuda, Yusaku Kumagai, Erin L. Fee, Michael Clarke, Matthew W. Kemp

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: The use of antenatal corticosteroids (ACS) in low-resource environments is sporadic. Further, drug choice, dose, and route of ACS are not optimized. We report the pharmacokinetics and pharmacodynamics of oral dosing of ACS using a preterm sheep model. Methods: We measured pharmacokinetics of oral betamethasone-phosphate (Beta-P) and dexamethasone-phosphate (Dex-P) using catheterized pregnant sheep. We compared fetal lung maturation responses of oral Beta-P and Dex-P to the standard treatment with 2 doses of the i.m. mixture of Beta-P and betamethasone-acetate at 2, 5, and 7 days after initiation of ACS. Results: Oral Dex-P had lower bioavailability than Beta-P, giving a lower maximum maternal and fetal concentration. A single oral dose of 0.33 mg/kg of Beta-P was equivalent to the standard clinical treatment assessed at 2 days; 2 doses of 0.16 mg/kg of oral Beta-P were equivalent to the standard clinical treatment at 7 days as assessed by lung mechanics and gas exchange after preterm delivery and ventilation. In contrast, oral Dex-P was ineffective because of its decreased bioavailability. Conclusion: Using a sheep model, we demonstrate the use of pharmacokinetics to develop oral dosing strategies for ACS. Oral dosing is feasible and may facilitate access to ACS in low-resource environments.

Original languageEnglish
JournalPediatric Research
DOIs
Publication statusE-pub ahead of print - 31 Jul 2019

Fingerprint

dexamethasone 21-phosphate
Sheep
Adrenal Cortex Hormones
Pharmacokinetics
Biological Availability
Lung
Mechanics
Ventilation
betamethasone sodium phosphate
Gases
Mothers
Pharmaceutical Preparations

Cite this

Schmidt, Augusto F. ; Jobe, Alan H. ; Kannan, Paranthaman S. ; Bridges, James P. ; Newnham, John P. ; Saito, Masatoshi ; Usuda, Haruo ; Kumagai, Yusaku ; Fee, Erin L. ; Clarke, Michael ; Kemp, Matthew W. / Oral antenatal corticosteroids evaluated in fetal sheep. In: Pediatric Research. 2019.
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abstract = "Background: The use of antenatal corticosteroids (ACS) in low-resource environments is sporadic. Further, drug choice, dose, and route of ACS are not optimized. We report the pharmacokinetics and pharmacodynamics of oral dosing of ACS using a preterm sheep model. Methods: We measured pharmacokinetics of oral betamethasone-phosphate (Beta-P) and dexamethasone-phosphate (Dex-P) using catheterized pregnant sheep. We compared fetal lung maturation responses of oral Beta-P and Dex-P to the standard treatment with 2 doses of the i.m. mixture of Beta-P and betamethasone-acetate at 2, 5, and 7 days after initiation of ACS. Results: Oral Dex-P had lower bioavailability than Beta-P, giving a lower maximum maternal and fetal concentration. A single oral dose of 0.33 mg/kg of Beta-P was equivalent to the standard clinical treatment assessed at 2 days; 2 doses of 0.16 mg/kg of oral Beta-P were equivalent to the standard clinical treatment at 7 days as assessed by lung mechanics and gas exchange after preterm delivery and ventilation. In contrast, oral Dex-P was ineffective because of its decreased bioavailability. Conclusion: Using a sheep model, we demonstrate the use of pharmacokinetics to develop oral dosing strategies for ACS. Oral dosing is feasible and may facilitate access to ACS in low-resource environments.",
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Oral antenatal corticosteroids evaluated in fetal sheep. / Schmidt, Augusto F.; Jobe, Alan H.; Kannan, Paranthaman S.; Bridges, James P.; Newnham, John P.; Saito, Masatoshi; Usuda, Haruo; Kumagai, Yusaku; Fee, Erin L.; Clarke, Michael; Kemp, Matthew W.

In: Pediatric Research, 31.07.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Oral antenatal corticosteroids evaluated in fetal sheep

AU - Schmidt, Augusto F.

AU - Jobe, Alan H.

AU - Kannan, Paranthaman S.

AU - Bridges, James P.

AU - Newnham, John P.

AU - Saito, Masatoshi

AU - Usuda, Haruo

AU - Kumagai, Yusaku

AU - Fee, Erin L.

AU - Clarke, Michael

AU - Kemp, Matthew W.

PY - 2019/7/31

Y1 - 2019/7/31

N2 - Background: The use of antenatal corticosteroids (ACS) in low-resource environments is sporadic. Further, drug choice, dose, and route of ACS are not optimized. We report the pharmacokinetics and pharmacodynamics of oral dosing of ACS using a preterm sheep model. Methods: We measured pharmacokinetics of oral betamethasone-phosphate (Beta-P) and dexamethasone-phosphate (Dex-P) using catheterized pregnant sheep. We compared fetal lung maturation responses of oral Beta-P and Dex-P to the standard treatment with 2 doses of the i.m. mixture of Beta-P and betamethasone-acetate at 2, 5, and 7 days after initiation of ACS. Results: Oral Dex-P had lower bioavailability than Beta-P, giving a lower maximum maternal and fetal concentration. A single oral dose of 0.33 mg/kg of Beta-P was equivalent to the standard clinical treatment assessed at 2 days; 2 doses of 0.16 mg/kg of oral Beta-P were equivalent to the standard clinical treatment at 7 days as assessed by lung mechanics and gas exchange after preterm delivery and ventilation. In contrast, oral Dex-P was ineffective because of its decreased bioavailability. Conclusion: Using a sheep model, we demonstrate the use of pharmacokinetics to develop oral dosing strategies for ACS. Oral dosing is feasible and may facilitate access to ACS in low-resource environments.

AB - Background: The use of antenatal corticosteroids (ACS) in low-resource environments is sporadic. Further, drug choice, dose, and route of ACS are not optimized. We report the pharmacokinetics and pharmacodynamics of oral dosing of ACS using a preterm sheep model. Methods: We measured pharmacokinetics of oral betamethasone-phosphate (Beta-P) and dexamethasone-phosphate (Dex-P) using catheterized pregnant sheep. We compared fetal lung maturation responses of oral Beta-P and Dex-P to the standard treatment with 2 doses of the i.m. mixture of Beta-P and betamethasone-acetate at 2, 5, and 7 days after initiation of ACS. Results: Oral Dex-P had lower bioavailability than Beta-P, giving a lower maximum maternal and fetal concentration. A single oral dose of 0.33 mg/kg of Beta-P was equivalent to the standard clinical treatment assessed at 2 days; 2 doses of 0.16 mg/kg of oral Beta-P were equivalent to the standard clinical treatment at 7 days as assessed by lung mechanics and gas exchange after preterm delivery and ventilation. In contrast, oral Dex-P was ineffective because of its decreased bioavailability. Conclusion: Using a sheep model, we demonstrate the use of pharmacokinetics to develop oral dosing strategies for ACS. Oral dosing is feasible and may facilitate access to ACS in low-resource environments.

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JF - Pediatric Research: international journal of human developmental biology

SN - 0031-3998

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