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J Clin Pharmacol. 2017 Feb;57(2):137-150. doi: 10.1002/jcph.804. Epub 2016 Sep 6.

Small-Molecule Compounds Exhibiting Target-Mediated Drug Disposition (TMDD): A Minireview.

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1
Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USA.

Abstract

Nonlinearities are commonplace in pharmacokinetics, and 1 special source is the saturable binding of the drug to a high-affinity, low-capacity target, a phenomenon known as target-mediated drug disposition (TMDD). Compared with large-molecule compounds undergoing TMDD, which has been well recognized due to its high prevalence, TMDD in small-molecule compounds is more counterintuitive and has not been well appreciated. With more and more potent small-molecule drugs acting on highly specific targets being developed as well as increasingly sensitive analytical techniques becoming available, many small-molecule compounds have recently been reported to have nonlinear pharmacokinetics imparted by TMDD. To expand our current knowledge of TMDD in small-molecule compounds and increase the awareness of this clinically important phenomenon, this minireview provides an overview of the small-molecule compounds that demonstrate nonlinear pharmacokinetics imparted by TMDD. The present review also summarizes the general features of TMDD in small-molecule compounds and highlights the differences between TMDD in small-molecule compounds and large-molecule compounds.

PMID:
27489162
DOI:
10.1002/jcph.804
[Indexed for MEDLINE]

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