In vitro methods to study the interplay of drug metabolism and efflux in the intestine.

Abstract:

:This review provides an overview of the in vitro methods currently used in studies of intestinal drug metabolism and active efflux with a special emphasis on the efflux- metabolism interplay. These methods include e.g. expressed enzymes or efflux transporters, fractionated intestinal cells, cell lines, primary cells, intestinal segments and other tissue preparations. Pharmacokinetics of effluxmetabolism interplay is often very complicated, possibly involving saturation, stimulation and/or inhibition of one or both of these mechanisms. Parent drug and/or metabolite(s) can be substrates for several enzymes and/or efflux proteins. These detoxifying proteins may alter the exposure of drugs to each other and, consequently, their contributions to the overall drug elimination. Depending on the complexity of the in vitro system used, different kinds of information can be extracted from the results. Simple methods concentrating on single mechanisms provide easily interpretable information, but neglect the interplay between various mechanisms influencing the kinetics in a whole organism. More complex experimental systems mimic the mechanistic complexity of in vivo setting better, but at the same time the interpretation and utilization of the results becomes more challenging. Advantages and limitations of various in vitro systems are addressed and consideration is given to the physiological relevance of the results obtained and there is discussion of approaches for in vitro - in vivo translation of the data.

journal_name

Curr Drug Metab

journal_title

Current drug metabolism

authors

Siissalo S,Heikkinen AT

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

102-11

issue

1

eissn

1389-2002

issn

1875-5453

pii

CDM-EPUB-20120409-005

journal_volume

14

pub_type

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