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Enhanced elimination of betamethasone in dichorionic twin pregnancies
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  • Grazielle Rodrigues,
  • Jhohann Benzi,
  • Luísa Matos,
  • Stella Freitas,
  • Maria Marques,
  • Ricardo Cavalli,
  • Elaine Moisés,
  • Geraldo Duarte,
  • Vera Lanchote,
  • Alessandra Marcolin
Grazielle Rodrigues
USP FMRP
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Jhohann Benzi
FCFRP-USP
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Luísa Matos
USP FMRP
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Stella Freitas
USP FMRP
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Maria Marques
FCFRP-USP
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Ricardo Cavalli
USP FMRP
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Elaine Moisés
USP FMRP
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Geraldo Duarte
USP FMRP
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Vera Lanchote
FCFRP-USP
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Alessandra Marcolin
USP FMRP
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Abstract

Aims: No study has evaluated the BET pharmacokinetics in twin pregnancies separated by chorionicity. The aim this study is to describe and compare the BET pharmacokinetic parameters in singleton, dichorionic (DC) and monochorionic (MC) twin pregnancies in the third trimester of pregnancy. Methods: Twenty-six pregnant women received an intramuscular dose of 6 mg of BET sodium phosphate plus 6 mg BET acetate. Serial blood samples were collected for 24 hours after the first intramuscular BET esters dose. BET plasma concentrations were quantified using a validated HPLC analytical method. BET pharmacokinetic parameters were obtained employing a non-compartment model, and were compared using ANOVA’s test with Tukey’s multiple comparisons test. Correlations between clinical features and pharmacokinetic parameters were analyzed using Pearson’s correlation. Preliminary data on the BET placental transfer were also presented. Results: The geometric mean (IC 95%) of AUC0-∞ 670.0 (504.3-805.2) vs 434.9 (311.2-539.6) ng.h/mL and the CL/F 18.38 (13.84-22.65) vs 29.40 (21.17-36.69) were significantly lower and higher, respectively, in DC twin pregnancies compared to singleton. Others pharmacokinetic parameters did not differ among the groups. Conclusions: Data from this study suggest that the presence of two fetoplacental units may increase the BET metabolism by CYP3A4 enzyme and increase its elimination. Pharmacokinetic-pharmacodynamic clinical studies are needed to investigate whether this BET pharmacokinetic changes have clinical repercussions for the newborns and require dose adjustment in DC twin pregnancies.

Peer review status:UNDER REVIEW

17 Mar 2021Submitted to British Journal of Clinical Pharmacology
18 Mar 2021Submission Checks Completed
18 Mar 2021Assigned to Editor
22 Mar 2021Reviewer(s) Assigned
06 Apr 2021Review(s) Completed, Editorial Evaluation Pending
06 Apr 2021Editorial Decision: Revise Major
01 Jun 20211st Revision Received
02 Jun 2021Submission Checks Completed
02 Jun 2021Assigned to Editor
02 Jun 2021Review(s) Completed, Editorial Evaluation Pending
08 Jun 2021Reviewer(s) Assigned