Effect of Body Fat on Population Pharmacokinetics of High‐Dose Methotrexate in Pediatric Patients with Acute Lymphoblastic Leukemia

2020 ◽  
Author(s):  
Etan Orgel ◽  
Teresa Nabais ◽  
Christopher Douglas ◽  
Steven D. Mittelman ◽  
Michael Neely
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Population Pharmacokinetics ◽  
Body Fat ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

scholarly journals Population Pharmacokinetics of High-Dose Methotrexate in Chinese Pediatric Patients With Acute Lymphoblastic Leukemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuan Gao ◽  
Xiao-Wen Qian ◽  
Xiao-Hua Zhu ◽  
Yi Yu ◽  
Hui Miao ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Lymphoblastic Leukemia ◽  
Serum Creatinine ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Concentration Data ◽  
Dose Methotrexate ◽  
Population Pk

High-dose methotrexate (HD-MTX) is widely used in pediatric acute lymphoblastic leukemia (ALL) treatment regimens. In this study, we aimed to develop a population pharmacokinetic (PK) model of HD-MTX in Chinese pediatric patients with ALL for designing personalized dosage regimens. In total, 4,517 MTX serum concentration data for 311 pediatric patients with ALL, aged 0.75–15.2 years and under HD-MTX treatment, were retrospectively collected at a tertiary Children’s Hospital in China. The non-linear mixed-effect model was used to establish the population PK model, using NONMEM software. The potential covariate effects of age, body weight, and biochemical measurements (renal and liver function) on MTX PK disposition were investigated. The model was then evaluated using goodness-of-fit, visual predictive check. MTX PK disposition was described using a three-compartment model reasonable well. Body weight, implemented as a fixed allometric function on all clearance and volume of distribution parameters, showed a substantial improvement in model fit. The final population model demonstrated that the MTX clearance estimate in a typical child with body weight of 19 kg was 6.9 L/h and the central distribution of volume estimate was 20.7 L. The serum creatinine significantly affected the MTX clearance, with a 0.97% decrease in clearance per 1 μmol/L of serum creatinine. Other covariates (e.g., age, sex, bilirubin, albumin, aspartate transaminase, concomitant medication) did not significantly affect PK properties of MTX. The proposed population PK model could describe the MTX concentration data in Chinese pediatric patients with ALL. This population PK model combined with a maximum a posteriori Bayesian approach could be used to estimate individual PK parameters, and optimize personalized MTX therapy in target patients, thus aiming to reduce toxicity and improve treatment outcomes.

scholarly journals Feasibility of Outpatient High-Dose Methotrexate Infusions in Pediatric Patients With B-Lineage Acute Lymphoblastic Leukemia

2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Joy L. Bartholomew, APRN ◽  
Hongying Dai, PhD ◽  
Keith J. August, MD, MS ◽  
Robin E. Ryan, MPH ◽  
Kristin A. Stegenga, PhD, RN, CPON
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
B Lineage

High-dose Methotrexate-induced Acral Erythema in Two Pediatric Patients With Acute Lymphoblastic Leukemia

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Kazuhiro Noguchi ◽  
Ryosei Nishimura ◽  
Yasuhiro Ikawa ◽  
Shintaro Mase ◽  
Toshihiro Fujiki ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Acral Erythema
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