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Drug Tissue Distribution: Study Methods and Therapeutic Implications

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Current interest in studies on tissue distribution stems from the limited capacity to predict tissue concentrations and the pharmacological response from plasma drug levels, and from the limitations - both methodological and deontological- involved in doing so, especially in humans. In this review we carry out a comparative analysis of the methods used for studying tissue distribution, placing special focus on recently developed noninvasive methods for the research of tissue distribution in humans, such as positron emission tomography and nuclear magnetic resonance spectroscopy. We describe the strategies of tissue distribution pharmacokinetic analysis that have evolved from analysis based on compartment and physiological models to analyses based on spatial and fractal models and, mainly, pharmacokinetic-pharmacodynamic models. Model-independent analysis based on the use of mean transit times or deconvolution strategies has become a good alternative for the pharmacokinetic analysis of tissue distribution. The need to increase the selectivity of many drugs justifies the desire to gain further insight into the design of new analogues prodrugs and carrier systems that will guarantee the specific delivery of a given drug to a particular organ or tissue, optimising the response. In silico models for drug distribution have become a helpful tool in drug discovery and development. The therapeutic implications of drug tissue distribution are also analysed, special reference being made to antiretroviral therapy and antitumoural gene therapy, among others.
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Keywords: drug development; drug tissue distribution; methods; pharmacokinetics; therapeutics

Document Type: Review Article

Affiliations: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Salamanca, Spain.

Publication date: November 1, 2005

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  • Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

    Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.
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