Journal article
Small-molecule compounds exhibiting target-mediated drug disposition - A case example of ABT-384
Journal of clinical pharmacology, Vol.55(10), pp.1079-1085
10/2015
DOI: 10.1002/jcph.531
PMID: 25931139
Abstract
Nonlinearities are frequently encountered in pharmacokinetics, and they can occur when 1 or more processes of absorption, distribution, metabolism, and excretion are saturable. One special source of nonlinearity that has been noticed recently is the saturable binding of the drug to a high-affinity-low-capacity target, a phenomenon known as target-mediated drug disposition (TMDD). Although TMDD can occur in both small-molecule compounds and large-molecule compounds, the latter has received much more attention because of its high prevalence. With the development of more potent small-molecule drugs acting on highly specific targets and the availability of increasingly sensitive analytical techniques, small-molecule compounds exhibiting TMDD have been increasingly reported in the past several years. ABT-384 is a small-molecule drug candidate that exhibited significant nonlinear pharmacokinetics, potentially imparted by TMDD, in a first-in-human clinical trial conducted in healthy volunteers. Compared with published small-molecule compounds exhibiting TMDD, ABT-384 pharmacokinetic characteristics are more consistent with TMDD. To expand current knowledge of TMDD of small-molecule compounds and increase awareness of this interesting and clinically important phenomenon, in this review the general features of small-molecule compounds exhibiting TMDD are highlighted, with ABT-384 provided as an example.
Details
- Title: Subtitle
- Small-molecule compounds exhibiting target-mediated drug disposition - A case example of ABT-384
- Creators
- Guohua An - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USAWei Liu - AbbVieSandeep Dutta - Clinical Pharmacology and Pharmacometrics, Research and Development, AbbVie, North Chicago, IL, USA
- Resource Type
- Journal article
- Publication Details
- Journal of clinical pharmacology, Vol.55(10), pp.1079-1085
- Publisher
- England
- DOI
- 10.1002/jcph.531
- PMID
- 25931139
- ISSN
- 0091-2700
- eISSN
- 1552-4604
- Language
- English
- Date published
- 10/2015
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984065317002771
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