دورية أكاديمية
أعرض في EDS

Population Pharmacokinetics of Fludarabine in Children and Adults during Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation.

التفاصيل البيبلوغرافية
العنوان: Population Pharmacokinetics of Fludarabine in Children and Adults during Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation.
المؤلفون: Langenhorst JB; Pediatric Blood and Marrow Transplant Program, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.; Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands., Dorlo TPC; Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands., van Maarseveen EM; Department of Clinical Pharmacy, University Medical Centre, Utrecht, Utrecht University, Heidelberglaan 100: D.00.X, 3584 CX, Utrecht, The Netherlands., Nierkens S; Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands., Kuball J; Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.; Department of Hematology, University Medical Centre, Utrecht, Utrecht University, Utrecht, The Netherlands., Boelens JJ; Pediatric Blood and Marrow Transplant Program, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.; Stem Cell Transplant and Cellular Therapies; Pediatrics, Memorial Sloan Kettering Cancer Centre, New York, NY, USA., van Kesteren C; Pediatric Blood and Marrow Transplant Program, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.; Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands., Huitema ADR; Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands. a.d.r.huitema-2@umcutrecht.nl.; Department of Clinical Pharmacy, University Medical Centre, Utrecht, Utrecht University, Heidelberglaan 100: D.00.X, 3584 CX, Utrecht, The Netherlands. a.d.r.huitema-2@umcutrecht.nl.
المصدر: Clinical pharmacokinetics [Clin Pharmacokinet] 2019 May; Vol. 58 (5), pp. 627-637.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Country of Publication: Switzerland NLM ID: 7606849 Publication Model: Print Cited Medium: Internet ISSN: 1179-1926 (Electronic) Linking ISSN: 03125963 NLM ISO Abbreviation: Clin Pharmacokinet Subsets: MEDLINE
أسماء مطبوعة: Publication: [Switzerland] : Adis, part of Springer Science+Business Media
Original Publication: New York, ADIS Press.
مواضيع طبية MeSH: Models, Biological*, Myeloablative Agonists/*pharmacokinetics , Vidarabine/*analogs & derivatives, Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Male ; Middle Aged ; Transplantation Conditioning ; Vidarabine/pharmacokinetics ; Young Adult
مستخلص: Background: Fludarabine is often used as an important drug in reduced toxicity conditioning regimens prior to hematopoietic cell transplantation (HCT). As no definitive pharmacokinetic (PK) basis for HCT dosing for the wide age and weight range in HCT is available, linear body surface area (BSA)-based dosing is still used.
Objective: We sought to describe the population PK of fludarabine in HCT recipients of all ages.
Methods: From 258 HCT recipients aged 0.3-74 years, 2605 samples were acquired on days 1 (42%), 2 (17%), 3 (4%) and 4 (37%) of conditioning. Herein, the circulating metabolite of fludarabine was quantified, and derived concentration-time data were used to build a population PK model using non-linear mixed-effects modelling.
Results: Variability was extensive where area under the curve ranged from 10 to 66 mg h/L. A three-compartment model with first-order kinetics best described the data. Actual body weight (BW) with standard allometric scaling was found to be the best body-size descriptor for all PK parameters. Estimated glomerular filtration rate (eGFR) was included as a descriptor of renal function. Thus, clearance was differentiated into a non-renal (3.24 ± 20% L/h/70 kg) and renal (eGFR × 0.782 ± 11% L/h/70 kg) component. The typical volumes of distribution of the central (V1), peripheral (V2), and second peripheral (V3) compartments were 39 ± 8%, 20 ± 11%, and 50 ± 9% L/70 kg respectively. Intercompartmental clearances between V1 and V2, and V1 and V3, were 8.6 ± 8% and 3.8 ± 13% L/h/70 kg, respectively.
Conclusion: BW and eGFR are important predictors of fludarabine PK. Therefore, current linear BSA-based dosing leads to highly variable exposure, which may lead to variable treatment outcome.
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معلومات مُعتمدة: P30 CA008748 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Myeloablative Agonists)
FA2DM6879K (Vidarabine)
P2K93U8740 (fludarabine)
تواريخ الأحداث: Date Created: 20181018 Date Completed: 20200708 Latest Revision: 20200827
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6451721
DOI: 10.1007/s40262-018-0715-9
PMID: 30327943
قاعدة البيانات: MEDLINE
الوصف
تدمد:1179-1926
DOI:10.1007/s40262-018-0715-9