{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:47:31Z","timestamp":1782283651985,"version":"3.54.5"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sertraline is widely used for the treatment of anxiety disorders in pediatric populations; however, substantial interindividual pharmacokinetic (PK) variability may significantly influence therapeutic efficacy and the occurrence of adverse events (AEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize the population PK profile of sertraline in pediatric patients with anxiety disorders and to evaluate its association with clinical response and AEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A prospective population PK study was conducted in 85 pediatric patients with anxiety disorders treated with sertraline monotherapy. Plasma concentrations were quantified using high-performance liquid chromatography with fluorescence detection. Population PK modeling was performed using nonlinear mixed-effects models (Monolix\u00ae). Anxiety severity was assessed using the Generalized Anxiety Disorder-7 (GAD-7) scale, and AEs were recorded throughout follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The mean dose was 35 \u00b1 15\u00a0mg\/day. High interindividual variability was observed in average plasma concentrations. Overall, 30.5% of patients experienced at least one adverse event, with nausea and insomnia being the most frequent. Patients with AEs exhibited lower apparent clearance and central volume of distribution, along with higher peak concentrations. Conversely, patients with greater anxiety severity showed higher clearance and lower steady-state average concentrations. An interquartile range of average concentrations (Cavg) between 27.85 and 57.91\u00a0ng\/mL was associated with a favorable balance between efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PK variability of sertraline is associated with differences in clinical response and AEs in pediatric patients. These findings suggest that systemic exposure to sertraline may be associated with clinical response and AEs, supporting the potential role of therapeutic drug monitoring and dose individualization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1862275","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:56:03Z","timestamp":1782280563000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exposure-response relationship of sertraline in pediatric patients with anxiety disorders: a population pharmacokinetic analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jesus Alonso","family":"Gandara Mireles","sequence":"first","affiliation":[{"name":"CIIDIR-Durango Unit, National Polytechnic Institute, Genomics Academy","place":["Durango, Mexico"]},{"name":"Latin American Network for the Implementation and Validation of Pharmacogenomic Clinical Guidelines 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