Enhanced elimination of betamethasone in dichorionic twin pregnancies

• Published in: British journal of clinical pharmacology 2022-02, Vol.88 (4), p.1897-1903
• Main Authors: Rodrigues, Grazielle de Fátima Pinto, Benzi, Jhohann Richard de Lima, Matos, Luísa Helena de Castro, Freitas, Stella Felippe, Marques, Maria Paula, Cavalli, Ricardo de Carvalho, Moisés, Elaine Christine Dantas, Duarte, Geraldo, Lanchote, Vera Lucia, Marcolin, Alessandra Cristina
• Format: Article
• Language: English
• Subjects: antenatal corticosteroids; betamethasone; CYP3A4; dichorionic twin pregnancy; monochorionic twin pregnancy; pharmacokinetics; placental transfer; pregnancy; twin pregnancy
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.15111

Aim No study has evaluated the betamethasone pharmacokinetics in twin pregnancies according to chorionicity. This study aimed to describe and compare the betamethasone pharmacokinetic parameters in singleton and dichorionic (DC) and monochorionic twin pregnancies in the third trimester of pregnancy. Methods Twenty‐six pregnant women received 2 intramuscular doses of 6 mg of betamethasone sodium phosphate plus 6 mg betamethasone acetate due to preterm labour. Serial blood samples were collected for 24 hours after the first intramuscular dose of betamethasone esters. Betamethasone plasma concentrations were quantified using a validated liquid chromatography–tandem mass spectrometry analytical method, and the pharmacokinetic parameters were obtained employing a noncompartmental model. Preliminary data on the betamethasone placental transfer are also presented. Results The geometric mean (95% confidence interval) of AUC0‐∞ 645.1 (504.3–825.2) vs. 409.8 (311.2–539.6) ng.h/mL and CL/F 17.70 (13.84–22.65) vs. 27.87 (21.17–36.69) were significantly different, respectively, in singleton pregnancies when compared to DC twins. Conclusion Data from this study suggest that the presence of 2 foetoplacental units may increase the betamethasone metabolism by hepatic CYP3A4 and/or placental 11β‐HSD2 enzymes. Pharmacokinetic–pharmacodynamic clinical studies are needed to investigate whether these betamethasone pharmacokinetic changes have clinical repercussions for the newborns and require dose adjustment in DC twin pregnancies.