{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:53:22Z","timestamp":1789502002035,"version":"build-2803163510"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To apply therapeutic drug monitoring and dose-individualization of intravenous Busulfan to paediatric patients and evaluate the impact of syringe-pump induced Busulfan infusion lag-time after in vitro estimation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>76 children and adolescents were administered 2 h intravenous Busulfan infusion every 6 h (16 doses). Busulfan plasma levels, withdrawn by an optimized sampling scheme and measured by a validated HPLC\u2013PDA method, were used to estimate basic PK parameters, AUC, Cmax, kel, t1\/2, applying Non-Compartmental Analysis. In vivo infusion lag-time was simulated in vitro and used to evaluate its impact on AUC estimation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Mean (%CV) Busulfan AUC, Cmax, clearance and t1\/2 for pediatric population were found 962.3 \u03bcm \u00d7 min (33.1), 0.95 mg\/L (41.4), 0.27 L\/h\/kg (33.3), 2.2 h (27.8), respectively. TDM applied to 76 children revealed 6 (7.9%) being above and 25 (32.9%) below therapeutic-range (AUC: 900\u20131350 \u03bcm \u00d7 min). After dose correction, all patients were measured below toxic levels (AUC &amp;lt; 1500 \u03bcm \u00d7 min), no patient below 900 \u03bcm \u00d7 min. Incorporation of infusion lag-time revealed lower AUCs with 17.1% more patients and 23.1% more younger patients, with body weight &amp;lt;16 kg, being below the therapeutic-range.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>TDM, applied successfully to 76 children, confirmed the need for Busulfan dose-individualization in paediatric patients. Infusion lag-time was proved clinically significant for younger, low body-weight patients and those close to the lower therapeutic-range limit.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgab087","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T19:18:40Z","timestamp":1621538320000},"page":"1340-1350","source":"Crossref","is-referenced-by-count":4,"title":["Dose individualization of intravenous busulfan in pediatric patients undergoing bone marrow transplantation: impact and <i>in vitro<\/i> evaluation of infusion lag-time"],"prefix":"10.1093","volume":"73","author":[{"given":"E","family":"Neroutsos","sequence":"first","affiliation":[{"name":"Laboratory of Biopharmaceutics & Pharmacokinetics, Department of Pharmacy, School of Health Sciences, National & Kapodistrian University of Athens , Athens 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Marrow Transplantation Unit, \u201cAgia Sophia\u201d General Children's Hospital of Athens , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Archontaki","sequence":"additional","affiliation":[{"name":"Laboratory of Analytical Chemistry, Department of Chemistry, School of Sciences, National & Kapodistrian University of Athens , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Tsirigotis","sequence":"additional","affiliation":[{"name":"Clinic of Internal Medicine, University Hospital \u201cAttikon\u201d, Department of Medicine, School of Health Sciences, National & Kapodistrian University of Athens , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Kitra","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Unit, \u201cAgia Sophia\u201d General Children's Hospital of Athens , Athens 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