Drug glucuronidation assays on human liver microsomes immobilized on microfluidic flow-through reactors

Iiro Kiiski, Elisa Ollikainen, Sanna Artes, Päivi Järvinen, Ville Jokinen, Tiina Sikanen

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Abstrakti

UDP-glucuronosyltransferases (UGTs), located in the endoplasmic reticulum of liver cells, are an important family of enzymes, responsible for the biotransformation of several endogenous and exogenous chemicals, including therapeutic drugs. However, the phenomenon of 'latency', i.e., full UGT activity revealed by disruption of the microsomal membrane, poses substantial challenges for predicting drug clearance based on in vitro glucuronidation assays. This work introduces a microfluidic reactor design comprising immobilized human liver microsomes to facilitate the study of UGT-mediated drug clearance under flow-through conditions. The performance of the microreactor is characterized using glucuronidation of 8-hydroxyquinoline (via multiple UGTs) and zidovudine (via UGT2B7) as the model reactions. With the help of alamethicin and albumin effects, we show that conducting UGT metabolism assays under flow conditions facilitates in-depth mechanistic studies, which may also shed light on UGT latency.

Alkuperäiskielienglanti
Artikkeli105677
LehtiEuropean Journal of Pharmaceutical Sciences
Vuosikerta158
Sivumäärä9
ISSN0928-0987
DOI - pysyväislinkit
TilaJulkaistu - 1 maalisk. 2021
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 116 Kemia
  • 317 Farmasia

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