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Enhanced elimination of betamethasone in dichorionic twin pregnancies
Author(s) -
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
Publication year - 2022
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.15111
Subject(s) - betamethasone , pharmacokinetics , medicine , pregnancy , fetus , confidence interval , obstetrics , endocrinology , biology , genetics
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 AUC 0‐∞ 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.