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Oral antenatal corticosteroids evaluated in fetal sheep

Schmidt, A.F., Jobe, A.H., Kannan, P.S., Bridges, J.P., Newnham, J.P., Saito, M., Usuda, H., Kumagai, Y., Fee, E.L., Clarke, M. and Kemp, M.W. (2019) Oral antenatal corticosteroids evaluated in fetal sheep. Pediatric Research, 86 .

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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

Item Type: Journal Article
Murdoch Affiliation(s): School of Veterinary and Life Sciences
Publisher: Nature Publishing Group
Copyright: © 2019, The Author(s)
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