{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T16:47:21Z","timestamp":1793810841545,"version":"4.6.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T00:00:00Z","timestamp":1599523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T00:00:00Z","timestamp":1599523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Alma Mater Studiorum - Universit\u00e0 di Bologna"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Clin Pharmacol"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>To characterize the post-marketing reporting of serotonin syndrome (SS) due to drug-drug interactions (DDIs) with linezolid and investigate the relationship with pharmacokinetic\/pharmacodynamic (PK\/PD) properties of serotonergic agents.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We queried the worldwide FDA Adverse Event Reporting System to extract SS records due to DDIs where linezolid was reported as suspect. For each serotonergic agent concomitantly reported, proportion of SS reports and mean number of DDIs were calculated and three different \u201cSS reporting zones\u201d were created. Relevant PK (peak concentration, area under plasma concentration curve, volume of distribution (V<jats:sub>D<\/jats:sub>), and lipophilicity) and PD (values of binding affinity (Ki) and IC<jats:sub>50<\/jats:sub> for serotonin reuptake transporter (SERT) and 5-HT<jats:sub>2A<\/jats:sub>) parameters were extracted for each serotonergic agent, and relevant PK\/PD indexes were calculated to assess correlation with mean number of DDIs (PV index).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Six hundred sixty-nine reports of SS mentioning linezolid were found, being linezolid-citalopram (<jats:italic>N<\/jats:italic> = 69; 10.3%) the most frequently DDI reported. Citalopram and methadone showed respectively the highest proportion of SS reports (0.28%) and the lowest mean number of DDIs (1.41). Citalopram, escitalopram, and methadone emerged as red (i.e., alert)-zone medications: they exhibited high lipophilicity and large V<jats:sub>D<\/jats:sub> (proxies of excellent central nervous system penetration) coupled with high potency. Among PK\/PD indexes, a significant correlation with PV index was found for V<jats:sub>D<\/jats:sub>\/Ki SERT ratio (<jats:italic>p<\/jats:italic> = 0.05).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>Our integrated approach suggests that linezolid is more likely to cause SS when co-administered with citalopram, escitalopram, and methadone, as inferred from their pharmacological properties. Proper management of SS should be tailored on a case-by-case basis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00228-020-02990-1","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T08:58:34Z","timestamp":1599728314000},"page":"233-239","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Serotonin syndrome by drug interactions with linezolid: clues from pharmacovigilance-pharmacokinetic\/pharmacodynamic analysis"],"prefix":"10.1007","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-3779","authenticated-orcid":false,"given":"Milo","family":"Gatti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0487-7996","authenticated-orcid":false,"given":"Emanuel","family":"Raschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0367-9595","authenticated-orcid":false,"given":"Fabrizio","family":"De Ponti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,8]]},"reference":[{"issue":"2","key":"2990_CR1","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1093\/jac\/dkw450","volume":"72","author":"A Zahedi Bialvaei","year":"2017","unstructured":"Zahedi Bialvaei A, Rahbar M, Yousefi M, Asgharzadeh M, Samadi KH (2017) Linezolid: a promising option in the treatment of Gram-positives. 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