{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:58:18Z","timestamp":1790621898542,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["107595\/Z\/15\/Z"],"award-info":[{"award-number":["107595\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["107\u2009595\/Z\/15\/Z"],"award-info":[{"award-number":["107\u2009595\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Cutaneous leishmaniasis (CL), a neglected infectious disease caused by the intracellular protozoan parasite\n                      <jats:italic>Leishmania<\/jats:italic>\n                      , affects over one million people annually. The type and magnitude of the inflammatory response elicited during infection lead to skin\u2010specific immunopathology, resulting in the clinical manifestations of CL. Systemic antileishmanial drugs are the main control measure; however, these are highly toxic, of long duration, and difficult to access for affected populations. New drugs and optimized regimens are urgently needed. Despite the known participation of immune responses in the pathology of CL, preclinical drug evaluations target parasite elimination as the efficacy measure. This overlooks the potential of host immune responses to influence therapeutic success.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we evaluated the performance of non\u2010linear pharmacokinetic\/pharmacodynamic (PK\/PD) models in recreating the exposure\u2013response relationships between plasma antimony (Sb) concentrations in CL patients treated with Glucantime (Sb\n                      <jats:sup>V<\/jats:sup>\n                      as meglumine antimoniate) and the gene expression dynamics of pro\u2010inflammatory mediators in peripheral blood mononuclear cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A one\u2010compartment PK model, coupled to an indirect PD model with endogenous regulators, fitted the data well, explaining 80%\u201390% of the variance. Our results suggest a mechanism of drug\u2010dependent immune gene regulation involving modulation of cell signalling and RNA stability in CL patients who have been cured after treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The model presented herein can be used for evaluating immune gene expression, alongside parasite kill, as PD endpoints of antileishmanials, both for new drug developments and in optimization of available drug regimens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70675","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T12:26:10Z","timestamp":1783081570000},"page":"3666-3675","source":"Crossref","is-referenced-by-count":0,"title":["Modelling immune gene expression profiles as pharmacodynamic endpoints of antileishmanial treatment"],"prefix":"10.1002","volume":"92","author":[{"given":"Neal","family":"Alexander","sequence":"first","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones M\u00e9dicas\u2010CIDEIM  Cali Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Giraldo\u2010Parra","sequence":"additional","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones M\u00e9dicas\u2010CIDEIM  Cali Colombia"},{"name":"Universidad Icesi  Cali Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Rebell\u00f3n\u2010S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones M\u00e9dicas\u2010CIDEIM  Cali Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8792-1563","authenticated-orcid":false,"given":"Mar\u00eda Adelaida","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones M\u00e9dicas\u2010CIDEIM  Cali Colombia"},{"name":"Universidad Icesi  Cali Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro862"},{"issue":"1","key":"e_1_2_11_3_1","first-page":"32","article-title":"Integrating pharmacokinetics, pharmacodynamics and pharmacogenomics to predict outcomes in antibacterial therapy","volume":"11","author":"Gumbo T","year":"2008","journal-title":"Curr Opin Drug Discov Devel"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1400352111"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2008.10.025"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002875"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/1469\u20100691.12556"},{"key":"e_1_2_11_8_1","unstructured":"PAHO.Pan American Health Organization. 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