Abstract
Background: Remdesivir was the first prodrug approved to treat coronavirus disease 2019 (COVID-19) and has the potential to be used during pregnancy. However, it is not known whether remdesivir and its main metabolite, GS-441524 have the potential to cross the blood-placental barrier. We hypothesize that remdesivir and predominant metabolite GS-441524may cross the blood-placental barrier to reach the embryo tissues.
Methods: To test this hypothesis, ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) coupled with multisite microdialysis was used to monitor the levels of remdesivir and the nucleoside analogue GS-441524 in the maternal blood, fetus, placenta, and amniotic fluid of pregnant Sprague-Dawley rats. The transplacental transfer was evaluated using the pharmacokinetic parameters of AUC and mother-to-fetus transfer ratio (AUC fetus /AUC mother ).
Findings: Our in-vivo results show that remdesivir is rapidly biotransformed into GS-441524 in the maternal blood, which then readily crossed the placenta with a mother-to-fetus transfer ratio of 0.51 ± 0.18. The C max and AUC last values of GS-441524 followed the order: maternal blood > amniotic fluid > fetus > placenta in rats.
Interpretation: While remdesivir does not directly cross into the fetus, however, its main metabolite, GS-441524 readily crosses the placenta and can reside there for at least 4 hours as shown in the pregnant Sprague-Dawley rat model. These findings suggest that careful consideration should be taken for the use of remdesivir in the treatment of COVID-19 in pregnancy.
Funding: Ministry of Science and Technology of Taiwan.
Keywords: Blood-placental barrier; GS-441524; Microdialysis; Pharmacokinetics; Remdesivir.
【저자키워드】 Remdesivir, pharmacokinetics, GS-441524, Blood-placental barrier, Microdialysis, 【초록키워드】 COVID-19, Treatment, coronavirus disease, Coronavirus disease 2019, mass spectrometry, Placenta, technology, Remdesivir, pharmacokinetics, Pregnancy, Liquid chromatography, Amniotic fluid, GS-441524, fetus, cross, Taiwan, metabolite, Blood, mother, pharmacokinetic, Tandem mass spectrometry, Microdialysis, Hypothesis, pregnant, AUC, during pregnancy, maternal blood, Science, placental barrier, tissues, RATs, transfer, nucleoside, treat, C max, while, MONITOR, parameter, UHPLC, shown, was used, evaluated, approved, predominant, amniotic, multisite, 【제목키워드】 Anti-viral, metabolite, pregnant, Biotransformation, transfer, predominant,