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J Cyst Fibros. 2015 Mar;14(2):178-81. doi: 10.1016/j.jcf.2014.10.007. Epub 2014 Nov 6.

A bioassay using intestinal organoids to measure CFTR modulators in human plasma.

Author information

1
Laboratory of Translational Immunology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
2
Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
3
Department of Pediatric Pulmonology, Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, The Netherlands.
4
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.

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.

KEYWORDS:

CFTR; Intestinal organoids; Personalized medicine; Pharmacokinetics; VX-770

PMID:
25467948
DOI:
10.1016/j.jcf.2014.10.007
[Indexed for MEDLINE]
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