{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:51:51Z","timestamp":1791971511065,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA040214"],"award-info":[{"award-number":["P30CA040214"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01A1 184132"],"award-info":[{"award-number":["U01A1 184132"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01A1 126612"],"award-info":[{"award-number":["U01A1 126612"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Thiotepa (TT) is often included in high\u2010dose chemotherapy prior to hematopoietic cell transplantation (HCT); however, exposure\u2013response relationships of TT and its primary metabolite, N,N',N''\u2010triethylenethiophosphoramide (TEPA), remain undefined. This was a prospective study enrolling children and young adults undergoing autologous and allogeneic HCT from multiple centers. Time\u2013concentration data were modeled using nonlinear mixed effects modeling along with clinical covariates potentially impacting pharmacokinetics. Cumulative area\u2010under\u2010the\u2010curve (cAUC) for TT and TEPA were derived using post hoc individual estimates for clearance. The combined cAUC\n                    <jats:sub>TT<\/jats:sub>\n                    and cAUC\n                    <jats:sub>TEPA<\/jats:sub>\n                    were also evaluated, reflecting total alkylating exposure (cAUC\n                    <jats:sub>total<\/jats:sub>\n                    ). The ratio of cAUC\n                    <jats:sub>TT<\/jats:sub>\n                    \/cAUC\n                    <jats:sub>TEPA<\/jats:sub>\n                    was used to evaluate the efficiency of metabolic conversion of TT to TEPA. A total of 91 subjects were included with a median (range) actual body weight and age of 16.7 kg (4.6\u2013110) and 4.5 years (0.23\u201322.5), respectively. The best fit model was a two\u2010compartment structure for TT, and a one\u2010compartment structure for TEPA. The conversion of TT to TEPA was found to be saturable at higher doses and may have important implications for optimizing exposure. Model\u2010based dosing, which accounts for age and body size, results in more predictive exposure as compared to conventional mg\/kg dosing, particularly in the very young and obese. Next steps include evaluation of pharmacogenomics and exposure\u2013response relationships to optimize dosing of TT in children.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70296","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:47:31Z","timestamp":1789804051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prospective Evaluation of Thiotepa Pharmacokinetics in Children and Young Adults Undergoing Allogeneic or Autologous Hematopoietic Cell Transplantation"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9060-9714","authenticated-orcid":false,"given":"Jordan","family":"Brooks","sequence":"first","affiliation":[{"name":"InsightRX  San Francisco CA 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Allergy Immunology, and Bone Marrow Transplantation University of California San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2702-4486","authenticated-orcid":false,"given":"Liusheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University of California San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4618-3813","authenticated-orcid":false,"given":"Christine","family":"Higham","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Allergy Immunology, and Bone Marrow Transplantation University of California San Francisco  San Francisco CA 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahal Rose","family":"Lalefar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California Davis  Davis CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3665-3102","authenticated-orcid":false,"given":"Eric","family":"Anderson","sequence":"additional","affiliation":[{"name":"Rady Children's Hospital of San Diego  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3030-8420","authenticated-orcid":false,"given":"Michael A.","family":"Pulsipher","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology Intermountain Primary Children's Hospital Huntsman Cancer Institute Spencer Fox Eccles School of Medicine and the University of Utah  Salt Lake City Utah 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