{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:18:52Z","timestamp":1784625532985,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Model\u2010informed precision dosing of tacrolimus is crucial to minimize toxicity and prevent graft\u2010\n                      <jats:italic>vs.\u2010<\/jats:italic>\n                      host disease in children undergoing haematopoietic stem cell transplantation (HSCT). Therefore, we developed a population pharmacokinetic model of tacrolimus oral suspension in paediatric HSCT patients that could be used for routine care.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixteen children receiving continuous intravenous (IV) tacrolimus who were switched to an oral suspension prepared at the hospital pharmacy were included. A total of 339 whole\u2010blood samples were collected and quantified by immunoassay: 260 during IV administration and 79 from 12\u2010h pharmacokinetic profiles (at 0, 20\u2009min, 1, 3 and 12\u2009h) after oral administration. Data analysis was performed using a nonlinear mixed\u2010effects approach with Monolix considering demographic, clinical and pharmacological factors as potential covariates influencing tacrolimus pharmacokinetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A 1\u2010compartment model with linear elimination adequately described tacrolimus pharmacokinetics. The typical estimated values (% relative standard error) for clearance, volume of distribution and absolute bioavailability were 1.5\u00a0L\/h (9.5%), 42.3\u00a0L (17.5%) and 40.0% (14.8%), respectively. A mean lag time of 0.3\u00a0h best characterized the delay in the absorption phase. Body weight was significantly associated with clearance, volume of distribution and bioavailability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A population pharmacokinetic model was developed to describe the pharmacokinetics of tacrolimus during continuous IV infusion or oral suspension administration in paediatric HSCT patients, which may be used for individualized dose adjustment. The mean bioavailability of the oral suspension was 40%, suggesting a dose conversion factor of 2.5 from IV to oral suspension therapy in our clinical setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70256","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T06:05:38Z","timestamp":1756274738000},"page":"210-219","source":"Crossref","is-referenced-by-count":1,"title":["Population pharmacokinetics and bioavailability of tacrolimus oral suspension in children with haematopoietic stem cell transplant"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6222-003X","authenticated-orcid":false,"given":"Lucas","family":"Brstilo","sequence":"first","affiliation":[{"name":"Unit of Innovative Treatments Hospital de Pediatr\u00eda JP Garrahan  Buenos Aires 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