{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T18:57:08Z","timestamp":1770490628047,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Clofarabine has recently been evaluated as part of the conditioning regimen for allogeneic hematopoietic stem cell transplantation (HCT) in children. Pharmacokinetic (PK) exposure of different agents commonly used in conditioning regimens is strongly related to HCT outcome. Consequently, the PK of clofarabine may be important for outcome. This report describes the population PK of clofarabine in paediatric patients and one adult.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From 80 paediatric (0.5\u201318 years) and 1 adult patient (37 years), 805 plasma concentrations were included in pharmacokinetic analyses using nonlinear mixed effects modelling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A two\u2010compartment model adequately described the PK of clofarabine. Body weight and estimated glomerular filtration rate (eGFR) were included as covariates. Clearance was differentiated into nonrenal and renal clearance (approximately 55% of total clearance), resulting in population estimates of 24.0 L\/h (95% confidence interval [CI] 13.7\u201334.4) and 29.8 L\/h (95% CI 23.9\u201336.1) for a patient of 70 kg with normal renal function, respectively. Unexplained interindividual variability in clearance was 17.8% (95% CI 14.6\u201322.4). A high variability in exposure was observed (range area under the curve<jats:sub>T0\u2010inf<\/jats:sub> 1.8\u20136.0 mg\/L*h) after body surface area (BSA) based dosing. Interestingly, children with low body weight had a lower exposure than children with a higher body weight, which indicates that the currently practised BSA\u2010based dosing is not adequate for clofarabine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A clofarabine dosing algorithm based on this PK model, using body weight and eGFR, results in a more predictable exposure than BSA\u2010based dosing. However, the exact target exposure needs to be further investigated.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14738","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T19:55:05Z","timestamp":1610740505000},"page":"3218-3226","source":"Crossref","is-referenced-by-count":7,"title":["Population pharmacokinetics of clofarabine for allogeneic hematopoietic cell transplantation in paediatric patients"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3448-7665","authenticated-orcid":false,"given":"A. Laura","family":"Nijstad","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Division of Laboratory Medicine and Pharmacy, University Medical Center Utrecht Utrecht University  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Nierkens","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht Utrecht University  Utrecht the Netherlands"},{"name":"Pediatric Blood and Bone Marrow Transplantation Princess M\u00e1xima Center for Pediatric Oncology  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline A.","family":"Lindemans","sequence":"additional","affiliation":[{"name":"Pediatric Blood and Bone Marrow Transplantation Princess M\u00e1xima Center for Pediatric Oncology  Utrecht the Netherlands"},{"name":"Department of Pediatrics, University Medical Center Utrecht Utrecht University  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaap Jan","family":"Boelens","sequence":"additional","affiliation":[{"name":"Pediatric Blood and Bone Marrow Transplantation Princess M\u00e1xima Center for Pediatric Oncology  Utrecht the Netherlands"},{"name":"Stem Cell Transplantation and Cellular Therapies, MSK Kids Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Bierings","sequence":"additional","affiliation":[{"name":"Pediatric Blood and Bone Marrow Transplantation Princess M\u00e1xima Center for Pediatric Oncology  Utrecht the Netherlands"},{"name":"Department of Pediatrics, University Medical Center Utrecht Utrecht University  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Birgitta","family":"Versluys","sequence":"additional","affiliation":[{"name":"Pediatric Blood and Bone Marrow Transplantation Princess M\u00e1xima Center for Pediatric Oncology  Utrecht the Netherlands"},{"name":"Department of Pediatrics, University Medical Center Utrecht Utrecht University  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim C.M.","family":"van der Elst","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Division of Laboratory Medicine and Pharmacy, University Medical Center Utrecht Utrecht University  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alwin D.R.","family":"Huitema","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Division of Laboratory Medicine and Pharmacy, University Medical Center Utrecht Utrecht University  Utrecht the Netherlands"},{"name":"Department of Pharmacy &amp; Pharmacology Netherlands Cancer Institute  Amsterdam the Netherlands"},{"name":"Department of Pharmacology Princess M\u00e1xima Center for Pediatric Oncology  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,2]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Genzyme Europe BV.Summary of Product Characteristics: Evoltra.2016.https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/evoltra-epar-product-information_en.pdf. Accessed January 18 2021."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.09.022"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270004269236"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-010-1376-z"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2019.04.017"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(16)30114-4"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018029421"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-014-0214-6"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2017.04.025"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5309.122"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.58.2.259"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.123553"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2004.02114.x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-008-0997-5"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2016.06.026"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9255-z"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9542-0"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2003.11.003"},{"key":"e_1_2_11_21_1","volume-title":"NONMEM User Guide. NONMEM Part V","author":"Boeckmann AJ","year":"2011"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2010.04.018"},{"key":"e_1_2_11_23_1","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2009"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14747"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra035092"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1989.7.11.1748"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0715-9"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12486"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.14738","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.14738","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.14738","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:11:34Z","timestamp":1693354294000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.14738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2]]},"references-count":27,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1111\/bcp.14738"],"URL":"https:\/\/doi.org\/10.1111\/bcp.14738","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2]]}}}