Fetal drug exposure after maternally administered CFTR modulators Elexacaftor/Tezacaftor/Ivacaftor in a rat model

Abstract

Background: The potential effects of the very effective cystic fibrosis triple combination drug, Elexacaftor/Tezacaftor/Ivacaftor (ETI) in pregnancy on prenatal development of offspring remain largely unknown. Research question: We aimed to investigate the fetal tissue distribution pattern of maternally administered ETI by placental transfer in the rat fetuses. Study design and methods: Sprague Dawley pregnant rats were administered ETI (6.7 mg/kg/d elexacaftor + 3.5 mg/kg/d tezacaftor + 25 mg/kg/d ivacaftor) traced with [3 H]-ivacaftor in single dose acute experiments (intraperitoneal injection) or treated orally with ETI (the same dose) for 7 days in sub-chronic experiments. Fetal tissue s..