The transplacental transfer of NHC, the active metabolite of molnupiravir, in the ex vivo human placental perfusion model

Pregnant patients with COVID-19 have an increased risk for negative outcomes such as preterm birth and low birth weight. Molnupiravir, an antiviral used to treat COVID-19, has limited data in pregnancy. Animal studies suggest embryotoxic and mutagenic potential, therefore placental transfer must be characterized to assess fetal risk. This medication may be necessary if the pregnant patient is critically ill. The objective of this study is to determine the rate and extent of placental transfer of molnupiravir. The transplacental pharmacokinetics of the active metabolite of molnupiravir, β-D-N4-hydroxycytidine (NHC), were determined using the ex vivo human placental perfusion model. NHC was introduced into the maternal circuit at therapeutic concentrations (2.97µg/mL) (n=4) or ten-times therapeutic concentrations (29.7 µg/mL) (n=4) and transfer was observed over three hours and then quantified by liquid chromatography mass spectrometry. NHC was detectable on the fetal side within 10 minutes. The average fetal:maternal concentration ratio was 0.48 for placentas perfused with 2.97 μg/mL, and 0.57 for those perfused with 29.7 μg/mL. These results suggest that significant concentrations of molnupiravir will reach the fetus and given the risk for teratogenicity, this therapeutic should be avoided in pregnancy unless maternal morbidity is severe and no safer alternatives exist.