{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:03:48Z","timestamp":1753869828220,"version":"3.41.2"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,10,12]],"date-time":"2016-10-12T00:00:00Z","timestamp":1476230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Asahi Kasei Pharma Co."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Thrombomodulin alfa (TM\u2010\u03b1) is a new class of anticoagulant drug for patients with disseminated intravascular coagulation (DIC). This study aimed to determine the pharmacokinetics of TM\u2010\u03b1 and determine the optimal dose in pediatric patients with hematological malignancy and DIC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Pediatric patients with hematological malignancy and DIC were administered TM\u2010\u03b1 at a dose of 0.06 mg\/kg (380 U\/kg) over 30 min every 24 hr. Blood samples were taken at steady state before the start, immediately after the end, and 24 hr after the start of the sixth administration. Population pharmacokinetic analysis was performed using sparse samples with the nonlinear mixed\u2010effect modeling program NONMEM<jats:sup>\u00ae<\/jats:sup>, version 7.3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The actual and predicted plasma concentrations of TM\u2010\u03b1 based on the final population pharmacokinetic model showed a good linear correlation. Clearance and volume of distribution of TM\u2010\u03b1 were affected by body weight. The clearance of TM\u2010\u03b1 in pediatric patients with hematological malignancy and DIC was higher than that in adults as previously reported. Six of eight patients did not achieve the target trough concentration at steady state. Furthermore, the pharmacokinetic simulation based on the estimated pharmacokinetic parameters from the final model demonstrated that TM\u2010\u03b1 administered at a dose of 0.06 mg\/kg every 24 hr also failed to achieve the target trough concentration at steady state in the majority of pediatric patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study shows that further dose adjustment of TM\u2010\u03b1 is necessary considering the higher clearance per body weight in pediatric patients with hematological malignancy and DIC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.26234","type":"journal-article","created":{"date-parts":[[2016,10,13]],"date-time":"2016-10-13T22:48:06Z","timestamp":1476398886000},"source":"Crossref","is-referenced-by-count":1,"title":["Population pharmacokinetics of thrombomodulin alfa in pediatric patients with hematological malignancy and disseminated intravascular coagulation"],"prefix":"10.1002","volume":"64","author":[{"given":"Masanobu","family":"Takeuchi","sequence":"first","affiliation":[{"name":"Department of Pediatrics Yokohama City University Hospital  Yokohama Japan"},{"name":"Division of Clinical Pharmacology and Toxicology The Hospital for Sick Children  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reo","family":"Tanoshima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yokohama City University Hospital  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoyuki","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Division of Hemato\u2010oncology\/Regenerative Medicine Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeo","family":"Sarashina","sequence":"additional","affiliation":[{"name":"Division of Hemato\u2010oncology\/Regenerative Medicine Kanagawa 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