Journal Article

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

Peppard, Thomas, Jusko, William J., Milad, Mark A., Jobe, Alan H.

2020

Overview

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.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Acetic acid / Administration, Oral / Adult / Age / Betamethasone - administration & dosage / Betamethasone - adverse effects / Betamethasone - analogs & derivatives / Betamethasone - pharmacokinetics / Chromatography / Cross-Over Studies / Dexamethasone / Dexamethasone - administration & dosage / Dexamethasone - adverse effects / Dexamethasone - pharmacokinetics / Dose-Response Relationship, Drug / Drug dosages / Drug Therapy, Combination - adverse effects / Drug Therapy, Combination - methods / FDA approval / Female / Fetuses / Glucocorticoids - administration & dosage / Glucocorticoids - adverse effects / Glucocorticoids - pharmacokinetics / Half-Life / Humans / India / Injections, Intramuscular / Leukocytes (basophilic) / Leukocytes (neutrophilic) / Lymphocytes / Mass spectrometry / Mortality / Neonates / Pharmacodynamics / Pharmacokinetics / Phosphate / Premature Birth - prevention & control / Prenatal Care - methods / Respiratory distress syndrome / Scientific imaging / Steroids / Substance abuse treatment