title: A bioassay using intestinal organoids to measure CFTR modulators in human plasma.
abstract: Treatment efficacies of drugs depend on patient-specific pharmacokinetic and pharmacodynamic properties. Here, we developed an assay to measure functional levels of the CFTR potentiator VX-770 in human plasma and observed that VX-770 in plasma from different donors induced variable CFTR function in intestinal organoids. This assay can help to understand variability in treatment response to CFTR potentiators by functionally modeling individual pharmacokinetics.
authors.affiliation: Laboratory of Translational Immunology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Dekkers
authors.affiliation: Laboratory of Translational Immunology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
authors.forename: L A W
authors.initials: LA
authors.lastname: Vijftigschild
authors.affiliation: Laboratory of Translational Immunology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Vonk
authors.affiliation: Laboratory of Translational Immunology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Kruisselbrink
authors.affiliation: Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
authors.forename: K M
authors.initials: KM
authors.lastname: de Winter-de Groot
authors.affiliation: Department of Pediatric Pulmonology, Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: Janssens
authors.affiliation: Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
authors.forename: C K
authors.initials: CK
authors.lastname: van der Ent
authors.affiliation: Laboratory of Translational Immunology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands; Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands. Electronic address: JBeekman@umcutrecht.nl.
authors.forename: J M
authors.initials: JM
authors.lastname: Beekman
mesh_terms: D000627:Aminophenols / Q000493:pharmacokinetics*; D016587:Antimutagenic Agents / Q000493:pharmacokinetics; D001681:Biological Assay; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D009154:Mutation / Q000187:drug effects; D009940:Organoids / Q000187:drug effects / Q000378:metabolism; D015363:Quinolones / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D000627:Aminophenols; D016587:Antimutagenic Agents; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor
keywords: CFTR; Intestinal organoids; Personalized medicine; Pharmacokinetics; VX-770