{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:05Z","timestamp":1787013905514,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This open\u2010label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony\u2010stimulating factor (PEG\u2010rhG\u2010CSF) for the treatment of chemotherapy\u2010induced neutropenia in children with acute leukaemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PEG\u2010rhG\u2010CSF was administered as a single 100 mcg\/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG\u2010rhG\u2010CSF. PEG\u2010rhG\u2010CSF serum concentrations were determined by an enzyme\u2010linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed\u2010effects model. Short\u2010term safety was evaluated through adverse events collection (registered at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link>\n                      identifier: 03844360).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 16 acute leukaemia patients (1.8\u201313.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG\u2010rhG\u2010CSF serum concentrations were obtainable. A one\u2010compartment model with first\u2010order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration\u2013time curve (AUC) were 5.65 (1.49\u201314.45) mL\/h\/kg and 16514.75 (6632.45\u201354423.30) ng\u00b7h\/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG\u2010rhG\u2010CSF was \u201cpossible\u201d.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The AUC of PEG\u2010rhG\u2010CSF (100 mcg\/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG\u2010rhG\u2010CSF (100 mcg\/kg) in children with sarcoma. PEG\u2010rhG\u2010CSF is safe, representing an important therapeutic option for chemotherapy\u2010induced neutropenia in paediatric patients with acute leukaemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.14750","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T16:59:00Z","timestamp":1611853140000},"page":"3292-3300","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacokinetics and safety of pegylated recombinant human granulocyte colony\u2010stimulating factor in children with acute leukaemia"],"prefix":"10.1111","volume":"87","author":[{"given":"Xi\u2010Ting","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Xia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang\u2010Wei","family":"Jia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Pharmacology Liaocheng People's Hospital  Liaocheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan\u2010Zhou","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Hua","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Liaocheng People's Hospital  Liaocheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue\u2010Qin","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Liaocheng People's Hospital  Liaocheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo\u2010Hao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Mei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Clinical Trial Center The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai\u2010Yan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Clinical Trial Center The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong\u2010Guo","family":"Sui","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Zhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Pharmacology Liaocheng People's Hospital  Liaocheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes N.","family":"van den Anker","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Children's National Medical Center  Washington District of Columbia USA"},{"name":"Departments of Pediatrics, Pharmacology &amp; 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