Journal article
Oral antenatal corticosteroids evaluated in fetal sheep
Pediatric Research, Vol.86
2019
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
Details
- Title
- Oral antenatal corticosteroids evaluated in fetal sheep
- Authors/Creators
- A.F. Schmidt (Author/Creator) - University of CincinnatiA.H. Jobe (Author/Creator) - University of CincinnatiP.S. Kannan (Author/Creator) - University of CincinnatiJ.P. Bridges (Author/Creator) - University of CincinnatiJ.P. Newnham (Author/Creator) - The University of Western AustraliaM. Saito (Author/Creator) - The University of Western AustraliaH. Usuda (Author/Creator) - Tohoku University HospitalY. Kumagai (Author/Creator) - Tohoku University HospitalE.L. Fee (Author/Creator) - The University of Western AustraliaM. Clarke (Author/Creator) - The University of Western AustraliaM.W. Kemp (Author/Creator) - Tohoku University Hospital
- Publication Details
- Pediatric Research, Vol.86
- Publisher
- Nature Publishing Group
- Identifiers
- 991005540014107891
- Copyright
- © 2019, The Author(s)
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
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- Citation topics
- 1 Clinical & Life Sciences
- 1.72 Obstetrics & Gynecology
- 1.72.924 Preterm Birth Causes
- Web Of Science research areas
- Pediatrics
- ESI research areas
- Clinical Medicine