{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T15:20:01Z","timestamp":1774106401141,"version":"3.50.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Maintaining amikacin concentrations within a specific therapeutic window is crucial to avoid sub-therapeutic or toxic levels. This study aimed to design a dosing nomogram for amikacin in neonates using a Population Pharmacokinetic (PopPK) modeling approach.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>PopPK model was developed using 101 amikacin concentrations from 80 neonates and validated using model diagnostics, and empirical Bayesian forecasting was performed. Pharmacokinetic profiles were simulated for virtual subjects with a range of covariates to identify suitable dosage regimens. Dosage regimens with the highest probability for the target group were selected to design the dosing nomogram.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>A two-compartment PK model best described the study data. Body weight (WT), serum creatinine (SCR), and post-natal age (PNA) affected the clearance of amikacin. The model predictions are with less than 15% absolute prediction error. WT and SCR were divided into five groups each, with each group repeated for every week of PNA for four weeks for dosing nomogram development.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>A PopPK model was developed and successfully-predicted concentrations in the study population. This model was used to develop a nomogram considering significant covariates like WT, SCR, and PNA. The proposed dosing nomogram can assist clinicians in developing individualized dosage regimens.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Impact<\/jats:title>\n            <jats:p>\n              <jats:list list-type=\"bullet\">\n                <jats:list-item>\n                  <jats:p>Population pharmacokinetic (PopPK) models for amikacin in term neonates were developed using clinical data from an Indian clinical setting and successfully-predicted the amikacin concentrations for the study population.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>Pharmacokinetic simulations with virtual subjects were used to calculate the probability of target attainment for different dosing regimens.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>The proposed dosing nomogram can potentially assist clinicians in designing optimal amikacin dosage regimens for neonates.<\/jats:p>\n                <\/jats:list-item>\n              <\/jats:list>\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1038\/s41390-025-04044-7","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T11:42:36Z","timestamp":1744285356000},"page":"936-941","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Precision dosing of amikacin in term neonates using pharmacometric approach"],"prefix":"10.1038","volume":"98","author":[{"given":"Saikumar","family":"Matcha","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaya Shree","family":"Dilli Batcha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun Prasath","family":"Raju","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhim Bahadur","family":"Chaudhari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudheer","family":"Moorkoth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surulivelrajan","family":"Mallayasamy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie E.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"4044_CR1","unstructured":"Doherty, T. 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(IEC- 558\/2019). We confirm that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Neonates were recruited into the study after obtaining consent from them.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}