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  <front>
    <journal-meta>
      <journal-id journal-id-type="iso-abbrev">Pharmacophore</journal-id>
      <journal-id journal-id-type="publisher-id">pharmacophorejournal.com</journal-id>
      <journal-id journal-id-type="publisher-id">Pharmacophore</journal-id>
      <journal-title-group>
        <journal-title>Pharmacophore</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2229-5402</issn>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">pharmacophorejournal.com-6931</article-id>
      <article-id pub-id-type="doi">10.51847/sdwKYP8O6t</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original research</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Drug Action Has an Address: Spatially Resolved Computational Pharmacology within Heterogeneous Tissue Microenvironments</article-title>
      </title-group>
                    <contrib-group>
                      <contrib contrib-type="author">
              <name>
                <surname>Dubois</surname>
                <given-names>Pierre</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                                            <xref rid="cor1" ref-type="corresp" />
                          </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Lefevre</surname>
                <given-names>Marc</given-names>
              </name>
                              <xref rid="aff2" ref-type="aff">2</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Moreau</surname>
                <given-names>Claire</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Martin</surname>
                <given-names>Julien</given-names>
              </name>
                              <xref rid="aff3" ref-type="aff">3</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Dupont</surname>
                <given-names>Thomas</given-names>
              </name>
                              <xref rid="aff4" ref-type="aff">4</xref>
                                        </contrib>
                  </contrib-group>
                  <aff id="aff1">
            <label>1</label>Department of Spatially Resolved Computational Pharmacology, Faculty of Pharmacy, University of Bordeaux, Bordeaux, France.
          </aff>
                  <aff id="aff2">
            <label>2</label>Department of Tissue Microenvironment and Drug Action, Faculty of Pharmacy, University of Nantes, Nantes, France.
          </aff>
                  <aff id="aff3">
            <label>3</label>Department of Heterogeneous Tissue Modeling, Faculty of Pharmacy, University of Strasbourg, Strasbourg, France.
          </aff>
                  <aff id="aff4">
            <label>4</label>Department of Spatial Drug Action and Addressability, Faculty of Pharmacy, Université Paris-Saclay, Paris, France.
          </aff>
                          <author-notes>
            <corresp id="cor1">
              <bold>Address for correspondence:</bold> Prof. Wael Abu Dayyih, Department of
              Pharmaceutical Chemistry, Faculty of Pharmacy, Mutah University, Al-Karak 61710, Jordan.
                              E-mail: <email xlink:href="pierre.dubois@u-bordeaux.fr">pierre.dubois@u-bordeaux.fr</email>
                          </corresp>
          </author-notes>
                    <pub-date pub-type="epub">
        <day>28</day>
        <month>08</month>
        <year>2026</year>
      </pub-date>
      <volume>17</volume>
      <issue>4</issue>
      <fpage>1</fpage>
      <lpage>12</lpage>
      <permissions>
        <copyright-statement>
          Copyright: &#x000a9; 2026 Pharmacophore
        </copyright-statement>
        <copyright-year>2026</copyright-year>
        <license>
          <ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/"
            specific-use="textmining" content-type="ccbyncsalicense">
            https://creativecommons.org/licenses/by-nc-sa/4.0/</ali:license_ref>
          <license-p>This is an open access journal, and articles are distributed under the terms of
            the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows
            others to remix, tweak, and build upon the work non-commercially, as long as appropriate
            credit is given and the new creations are licensed under the identical terms.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>A<sc>BSTRACT</sc></title>
        <p>Pharmacological action is conventionally summarized through systemic exposure, tissue-average concentration, target expression, or aggregate response, yet each of these measures can obscure the local conditions that determine whether a drug reaches, engages, and alters a biologically relevant tissue state. This article develops a proposed Spatially Resolved Computational Pharmacology Architecture for representing drug action as an address-dependent process within heterogeneous microenvironments. The approach integrates coordinate-resolved exposure, transport, target accessibility, cell identity, tissue state, target engagement, response, resistance, toxicity, uncertainty, and whole-body coupling while preserving the evidentiary distinctions among measured, inferred, and simulated quantities. The synthesis argues that no single performance metric can establish spatial pharmacological adequacy because local action depends on the interaction of delivery, binding, cellular composition, structural barriers, adaptive dynamics, and temporal context. The central contribution is an architecture that assigns explicit data contracts, uncertainty boundaries, and validation obligations to each component, thereby preventing spatial maps, omics-derived states, and mechanistic simulations from being treated as interchangeable evidence. The article further distinguishes spatial association from mechanism, local exposure from pharmacologically available concentration, target expression from engagement, and benchmark performance from prospective pharmaceutical usefulness. Important limitations include incomplete tissue sampling, cross-platform registration error, uncertain scale translation, sparse longitudinal measurements, parameter non-identifiability, and restricted evidence outside intensively studied disease settings. The proposed architecture is therefore not a validated predictive system or clinical decision tool. Its value lies in organizing testable questions, guiding multimodal evidence integration, and defining the conditions under which localized and systemic therapies may be evaluated with greater spatial and mechanistic discipline.</p>
      </abstract>
      <kwd-group>
                <kwd>Spatial pharmacology</kwd>
                <kwd>Tissue microenvironment</kwd>
                <kwd>Spatial omics</kwd>
                <kwd>Drug distribution</kwd>
                <kwd>Target engagement</kwd>
                <kwd>Transport modelling</kwd>
              </kwd-group>
    </article-meta>
  </front>
</article>