Maternal-Fetal Letermovir Exposure in Vivo and PBPK-based: A Rationale for Congenital CMV Therapy.
case_series · Level IV
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- Record sourced from PubMed, PMID 41403238.
- Also identified by DOI 10.1093/infdis/jiaf619.
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Abstract
Cytomegalovirus (CMV) affects 0.5-2.0% of all live births and is the main nongenetic cause of congenital sensorineural hearing loss and neurological damage, yet no validated prenatal treatment exists for infected fetuses. Letermovir, a CMV-specific antiviral, is approved for prophylaxis in transplant recipients. This study aimed to quantify maternal-fetal exposure to letermovir following maternal administration, focusing on CMV-target fetal organs, particularly the brain. Seven pregnant women undergoing second-trimester termination of pregnancy for fetal anomalies received oral letermovir (240 or 480 mg once daily) for three days. On the day of termination, samples from maternal and fetal blood, placenta, and fetal organs were collected and analyzed. Plasma and tissue drug concentrations were compared to the EC50Letermovir to assess potential antiviral efficacy. Letermovir achieved therapeutic levels in all compartments. Complementary physiologically-based-pharmacokinetic modeling confirmed adequate fetal exposure across pregnancy stages. No maternal adverse events were observed. These unique in vivo data provide the first pharmacological rationale supporting letermovir use during pregnancy for congenital CMV therapy.