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Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver.

ABSTRACT: Intracellular concentrations of drugs and metabolites are often important determinants of efficacy, toxicity, and drug interactions. Hepatic drug distribution can be affected by many factors, including physicochemical properties, uptake/efflux transporters, protein binding, organelle sequestration, and metabolism. This white paper highlights determinants of hepatocyte drug/metabolite concentrations and provides an update on model systems, methods, and modeling/simulation approaches used to quantitatively assess hepatocellular concentrations of molecules. The critical scientific gaps and future research directions in this field are discussed.

SUBMITTER: Chu X

PROVIDER: S-EPMC3898878 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver.

Chu X X Korzekwa K K Elsby R R Fenner K K Galetin A A Lai Y Y Matsson P P Moss A A Nagar S S Rosania G R GR Bai J P F JP Polli J W JW Sugiyama Y Y Brouwer K L R KL

Clinical pharmacology and therapeutics 20130410 1

Intracellular concentrations of drugs and metabolites are often important determinants of efficacy, toxicity, and drug interactions. Hepatic drug distribution can be affected by many factors, including physicochemical properties, uptake/efflux transporters, protein binding, organelle sequestration, and metabolism. This white paper highlights determinants of hepatocyte drug/metabolite concentrations and provides an update on model systems, methods, and modeling/simulation approaches used to quant ...[more]

PMID: 23588320

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