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 fun...

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Bibliographic Details
Published in:Journal of cystic fibrosis 2015-03, Vol.14 (2), p.178-181
Main Authors: Dekkers, R, Vijftigschild, L.A.W, Vonk, A.M, Kruisselbrink, E, de Winter-de Groot, K.M, Janssens, H.M, van der Ent, C.K, Beekman, J.M
Format: Article
Language:English
Subjects:
Aminophenols - pharmacokinetics
Antimutagenic Agents - pharmacokinetics
Biological Assay
CFTR
Cystic Fibrosis - drug therapy
Cystic Fibrosis - genetics
Cystic Fibrosis - physiopathology
Cystic Fibrosis Transmembrane Conductance Regulator - genetics
Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
Drug Monitoring - methods
Humans
Intestinal organoids
Intestines - metabolism
Intestines - pathology
Mutation - drug effects
Organoids - drug effects
Organoids - metabolism
Personalized medicine
Pharmacokinetics
Pulmonary/Respiratory
Quinolones - pharmacokinetics
Treatment Outcome
VX-770
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Summary: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.
ISSN:1569-1993
1873-5010
DOI:10.1016/j.jcf.2014.10.007