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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-6965</article-id>
      <article-id pub-id-type="doi">10.51847/ZY5oDJBhRo</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original research</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>The Dose Twin: Simulating Individualized Treatment under Changing Physiology, Disease Progression, Adherence, and Therapeutic Response</article-title>
      </title-group>
                    <contrib-group>
                      <contrib contrib-type="author">
              <name>
                <surname>Otieno</surname>
                <given-names>Peter</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                                            <xref rid="cor1" ref-type="corresp" />
                          </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Atieno</surname>
                <given-names>Grace</given-names>
              </name>
                              <xref rid="aff2" ref-type="aff">2</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Okoth</surname>
                <given-names>Felix</given-names>
              </name>
                              <xref rid="aff3" ref-type="aff">3</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Moraa</surname>
                <given-names>Caroline</given-names>
              </name>
                              <xref rid="aff4" ref-type="aff">4</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Müller</surname>
                <given-names>Thomas</given-names>
              </name>
                              <xref rid="aff5" ref-type="aff">5</xref>
                                        </contrib>
                  </contrib-group>
                  <aff id="aff1">
            <label>1</label>Department of Dose Twin and Individualized Treatment Simulation, Faculty of Pharmacy, Kenya Medical Research Institute, Kisumu, Kenya.
          </aff>
                  <aff id="aff2">
            <label>2</label>Department of Changing Physiology and Disease Progression, Faculty of Pharmacy, University of Nairobi, Nairobi, Kenya.
          </aff>
                  <aff id="aff3">
            <label>3</label>Department of Adherence and Therapeutic Response Modeling, Faculty of Pharmaceutical Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
          </aff>
                  <aff id="aff4">
            <label>4</label>Department of Personalized Dose Simulation, Faculty of Pharmacy, Moi University, Eldoret, Kenya.
          </aff>
                  <aff id="aff5">
            <label>5</label>Department of Treatment Optimization and Digital Twins, Faculty of Veterinary Medicine, University of Zurich, Zurich, Switzerland.
          </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="peter.otieno@kemri.go.ke">peter.otieno@kemri.go.ke</email>
                          </corresp>
          </author-notes>
                    <pub-date pub-type="epub">
        <day>28</day>
        <month>04</month>
        <year>2025</year>
      </pub-date>
      <volume>16</volume>
      <issue>2</issue>
      <fpage>53</fpage>
      <lpage>64</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>Drug dosing is commonly initiated from population evidence and refined through covariates, therapeutic drug monitoring, pharmacokinetic–pharmacodynamic models, or clinician judgment. These approaches remain essential, but they do not necessarily provide a unified representation of an individual whose physiology, disease state, treatment adherence, drug exposure, therapeutic response, and toxicity risk change concurrently. This article proposes the Dose Twin, a patient-linked and time-indexed computational pharmacology decision model for reconstructing actual treatment, estimating evolving pharmacological and disease states, and comparing bounded counterfactual dose regimens. The construct integrates population priors with longitudinal patient observations while preserving explicit distinctions among measured variables, latent states, mechanistic assumptions, learned components, uncertainty, and clinical decisions. Its proposed architecture contains a treatment-history reconstruction layer, dynamic physiology and disease representations, a pharmacokinetic–pharmacodynamic or quantitative systems pharmacology core, an adherence model, a sequential updating mechanism, a counterfactual dose evaluator, safety and uncertainty gates, and a clinician authorization layer. The central contribution is not a new optimization metric or autonomous dosing algorithm, but an organizing decision model that treats individualized dosing as repeated inference under changing and incompletely observed conditions. It also prevents apparent treatment failure from being attributed automatically to altered pharmacology when missed doses, delayed administration, disease progression, measurement error, or model misspecification remain plausible explanations. The Dose Twin is presented as a conceptual and methodological contribution requiring context-specific technical verification, pharmacological validation, prospective clinical evaluation, workflow assessment, and governance. It does not establish individual causal effects, clinical benefit, regulatory acceptability, or deployment readiness. Its value lies in defining what must be represented, updated, tested, bounded, and communicated before longitudinal treatment simulation can responsibly influence model-informed precision dosing.</p>
      </abstract>
      <kwd-group>
                <kwd>Model-informed precision dosing</kwd>
                <kwd>Computational pharmacology</kwd>
                <kwd>Digital twin</kwd>
                <kwd>Longitudinal pharmacokinetics</kwd>
                <kwd>Treatment adherence</kwd>
                <kwd>Counterfactual simulation</kwd>
              </kwd-group>
    </article-meta>
  </front>
</article>