{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:04:34Z","timestamp":1783915474954,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>\n                    Piperacillin\u2013tazobactam is frequently used in children undergoing liver transplantation (LT), yet its pharmacokinetics (PK) in this population remains poorly characterized. We aimed to develop a population pharmacokinetic model for piperacillin in plasma and peritoneal fluid in children undergoing LT and to optimize dosing regimen for this population. We conducted a retrospective, single\u2010center, observational study including all children receiving piperacillin\u2013tazobactam as prophylaxis for LT and had at least one piperacillin concentration in both plasma and peritoneal fluid. PK analysis was conducted using nonlinear mixed effect modeling (Monolix) and was part of Optimome study. We included 31 patients with a median (range) age of 4\u2009years (4\u2009months\u201317\u2009years). A total of 172 plasma and 146 peritoneal fluid samples were analyzed. Plasma concentrations were best fitted by a one\u2010compartment model with first\u2010order elimination. A virtual effect site compartment was added to adequately describe piperacillin concentrations in plasma and peritoneal fluid. Allometrically scaled body weight (pre\u2010transplant and current values) and glomerular filtration rate (eGFR) were identified as significant covariates. Median (range) peritoneal\/plasma AUC\n                    <jats:sub>0\u201324h<\/jats:sub>\n                    ratio was 72 (45\u201394) %. Simulations showed that optimal dosing regimens ranged from 300\u2009mg\/kg\/day (q6h over 3\u2009hours) to 400\u2009mg\/kg\/day as a continuous infusion, depending on the PK target (i.e.,\n                    <jats:italic>f<\/jats:italic>\n                    T\n                    <jats:sub>&gt;1\u2009\u00d7\u2009MIC<\/jats:sub>\n                    or\n                    <jats:italic>f<\/jats:italic>\n                    T\n                    <jats:sub>&gt;4\u2009\u00d7\u2009MIC<\/jats:sub>\n                    ) and patient eGFR. In children undergoing LT, body weight and renal function explained some of the between subject variability for piperacillin PK. Higher dosing regimen combined with therapeutic drug monitoring is necessary to optimize exposure in plasma and at surgical site.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70346","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T04:01:07Z","timestamp":1780113667000},"page":"484-491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Piperacillin Population Pharmacokinetics in Plasma and Peritoneal Fluid and Dosing Optimization in Children Undergoing Liver Transplant: An Optimome Study"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4280-4683","authenticated-orcid":false,"given":"No\u00e9mie","family":"de Cacqueray","sequence":"first","affiliation":[{"name":"Service R\u00e9animation et Soins Intensifs Polyvalents P\u00e9diatriques \u2010 SMUR p\u00e9diatrique AP\u2010HP, H\u00f4pital Necker Enfants Malades  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, UMR1343, Pharmacologie et \u00c9valuations des Th\u00e9rapeutiques Chez l'Enfant et la Femme Enceinte  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0488-5948","authenticated-orcid":false,"given":"Mehdi","family":"Oualha","sequence":"additional","affiliation":[{"name":"Service R\u00e9animation et Soins Intensifs Polyvalents P\u00e9diatriques \u2010 SMUR p\u00e9diatrique AP\u2010HP, H\u00f4pital Necker Enfants Malades  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, UMR1343, Pharmacologie et \u00c9valuations des Th\u00e9rapeutiques Chez l'Enfant et la Femme Enceinte  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3950-7728","authenticated-orcid":false,"given":"Frantz","family":"Foissac","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, UMR1343, Pharmacologie et \u00c9valuations des Th\u00e9rapeutiques Chez l'Enfant et la Femme Enceinte  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo Froelicher","family":"Bournaud","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, UMR1343, Pharmacologie et \u00c9valuations des Th\u00e9rapeutiques Chez l'Enfant et la Femme Enceinte  Paris France"},{"name":"Service Pharmacologie clinique, AP\u2010HP, H\u00f4pital Cochin  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6529-0024","authenticated-orcid":false,"given":"Gabrielle","family":"Lui","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, UMR1343, Pharmacologie et \u00c9valuations des Th\u00e9rapeutiques Chez l'Enfant et la Femme Enceinte  Paris France"},{"name":"Service Pharmacologie clinique, AP\u2010HP, H\u00f4pital Cochin  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Bille","sequence":"additional","affiliation":[{"name":"Service Microbiologie, AP\u2010HP, H\u00f4pital Necker Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Chardot","sequence":"additional","affiliation":[{"name":"Service Chirurgie p\u00e9diatrique, Transplantation, AP\u2010HP, H\u00f4pital Necker Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5791-5402","authenticated-orcid":false,"given":"Carmen","family":"Capito","sequence":"additional","affiliation":[{"name":"Service Chirurgie p\u00e9diatrique, Transplantation, AP\u2010HP, H\u00f4pital Necker Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lacaille","sequence":"additional","affiliation":[{"name":"Service Gastroent\u00e9rologie\u2010Nutrition p\u00e9diatriques et Unit\u00e9 d'H\u00e9patologie Transplantation P\u00e9diatrique, AP\u2010HP, H\u00f4pital Necker Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippine","family":"Widmer","sequence":"additional","affiliation":[{"name":"Service R\u00e9animation et Soins Intensifs Polyvalents P\u00e9diatriques \u2010 SMUR p\u00e9diatrique AP\u2010HP, H\u00f4pital Necker Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Toubiana","sequence":"additional","affiliation":[{"name":"Service P\u00e9diatrie G\u00e9n\u00e9rale et Maladies Infectieuses, AP\u2010HP, H\u00f4pital Necker Enfants Malades  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Institut Pasteur, Biodiversit\u00e9 et \u00c9pid\u00e9miologie des Infections Bact\u00e9rienne  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Marc","family":"Tr\u00e9luyer","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, UMR1343, Pharmacologie et \u00c9valuations des Th\u00e9rapeutiques Chez l'Enfant et la Femme Enceinte  Paris France"},{"name":"Service Pharmacologie clinique, AP\u2010HP, H\u00f4pital Cochin  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihem","family":"Benaboud","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, UMR1343, Pharmacologie et \u00c9valuations des Th\u00e9rapeutiques Chez l'Enfant et la Femme Enceinte  Paris France"},{"name":"Service Pharmacologie clinique, AP\u2010HP, H\u00f4pital Cochin  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na\u00efm","family":"Bouazza","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, UMR1343, Pharmacologie et \u00c9valuations des Th\u00e9rapeutiques Chez l'Enfant et la Femme Enceinte  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France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000023169"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000002662"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.13589"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp120568"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.1333"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0682-1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2021.10.013"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.PCC.0000149131.72248.E6"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31828a2bbd"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-013-2426-7"},{"key":"e_1_2_10_11_1","unstructured":"Prescribing 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