New dosing nomogram and population pharmacokinetic model for young and very young children receiving busulfan for hematopoietic stem cell transplantation conditioning
| Autor: | Eva de Berranger, Olivier Mir, Angelo Paci, Véronique Kemmel, Philippe Bourget, Claire Galambrun, Virginie Gandemer, Charlotte Jubert, Christelle Dufour, Despina Moshous, Vianney Poinsignon, Bénédicte Devictor, Laurent Nguyen, Laura Faivre, Jean-Hugues Dalle, Gilles Vassal, Aurélie Pétain, J.P. Vannier, Sabrina Bondu, Sophie Broutin, Bénédicte Neven |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Pediatrics medicine.medical_specialty Transplantation Conditioning medicine.medical_treatment Population Hematopoietic stem cell transplantation 03 medical and health sciences 0302 clinical medicine Pharmacokinetics medicine Humans Tissue Distribution Dosing education Busulfan education.field_of_study Models Statistical medicine.diagnostic_test Dose-Response Relationship Drug business.industry Area under the curve Hematopoietic Stem Cell Transplantation Infant Hematology Nomogram Myeloablative Agonists Prognosis Combined Modality Therapy Nomograms Oncology Therapeutic drug monitoring 030220 oncology & carcinogenesis Hematologic Neoplasms Pediatrics Perinatology and Child Health Female Drug Monitoring business 030215 immunology medicine.drug Follow-Up Studies |
| Zdroj: | Pediatric bloodcancerREFERENCES. 67(10) |
| ISSN: | 1545-5017 |
| Popis: | BACKGROUND Busulfan (Bu) is the cornerstone of conditioning regimens prior to hematopoietic stem cell transplantation, widely used in both adults and children for the treatment of malignant and nonmalignant diseases. Despite an intravenous formulation, interindividual variability (IIV) remains high and optimal exposure difficult to achieve, especially in neonates and infants. PROCEDURE To ensure both efficacy and safety, we set up in 2005 an observational study designed for children not fully assessed during the drug registration procedure. From a large cohort of 540 patients, we developed a Bu population pharmacokinetic model based on body weight (BW) and maturation concepts to reduce IIV and optimize exposure. A new dosing nomogram was evaluated to better fit the population pharmacokinetic model. RESULTS Bu clearance IIV was significantly decreased from 61.3% (covariate-free model) to 28.6% when combining BW and maturation function. Median Bu area under the curve (AUC) was 1179 µmol/L × min compared to 1025 with the EMA dosing nomogram for children |
| Databáze: | OpenAIRE |
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