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Pediatr Res. 2019 Nov;86(5):589-594. doi: 10.1038/s41390-019-0519-0. Epub 2019 Jul 31.

Oral antenatal corticosteroids evaluated in fetal sheep.

Author information

1
Division of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
2
Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA.
3
Division of Obstetrics and Gynecology, The University of Western Australia, Perth, WA, Australia.
4
Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, 980-8574, Japan.
5
Metabolomics Australia, Centre for Microscopy, Characterization and Analysis, The University of Western Australia, Perth, WA, Australia.
6
Division of Obstetrics and Gynecology, The University of Western Australia, Perth, WA, Australia. matthew.kemp@uwa.edu.
7
Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, 980-8574, Japan. matthew.kemp@uwa.edu.
8
School of Veterinary and Life Sciences, Murdoch University, Perth, WA, Australia. matthew.kemp@uwa.edu.

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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