Intracellular Drug Concentrations and Transporters: Measurement, Modeling, and Implications for the Liver.
Chu, X 1; Korzekwa, K 2; Elsby, R 3; Fenner, K 3; Galetin, A 4; Lai, Y 5,13; Matsson, P 6; Moss, A 7; Nagar, S 2; Rosania, G R 8; Bai, J PF 9; Polli, J W 10; Sugiyama, Y 11; Brouwer, K LR 12; on behalf of the International Transporter Consortium
[Review]
Clinical Pharmacology & Therapeutics.
94(1):126-141, July 2013.
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: 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.
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