Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies
Само за регистроване кориснике
2024
Аутори
Škorić, BiljanaJovanović, Marija
Kuzmanović, Miloš
Miljković, Branislava
Vučićević, Katarina
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Purpose: The aim of the present study was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) and to describe the influence of variability factors. Methods: The study included 50 patients of both sexes (aged 1–18 years) who received 3 or 5 g/m2 of HDMTX. A nonlinear mixed effect modeling approach was applied for data analysis. Parameter estimation was performed by first-order conditional estimation method with interaction (FOCEI), whereas stepwise covariate modeling was used to assess variability factors. Results: The final model is a two-compartment model that incorporates the effect of body surface area and the influence of hemoglobin and serum creatinine on MTX clearance (CL). Population pharmacokinetic values for a typical subject were estimated at 5.75 L/h/m2 for clearance (CL), 21.3 L/m2 for volume of the central compartment (V1), 8.2 ...L/m2 for volume of the peripheral compartment (V2), and 0.087 L/h/m2 for intercompartmental clearance (Q). According to the final model, MTX CL decreases with increasing serum creatinine, whereas a positive effect was captured for hemoglobin. A difference of almost 32% in MTX CL was observed among patients’ hemoglobin values reported in the study. Conclusion: The developed population pharmacokinetic model can contribute to the therapy optimization during HDMTX in pediatric patients with ALL and NHL. In addition to renal function and body weight, it describes the influence of hemoglobin on CL, allowing better understanding of its contribution to the disposition of HDMTX.
Кључне речи:
Pharmacokinetic variability / Children / Covariate analysis / Methotrexate / NONMEM / Therapeutic drug monitoringИзвор:
European Journal of Clinical Pharmacology, 2024Издавач:
- Springer Science and Business Media Deutschland GmbH
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
DOI: 10.1007/s00228-024-03642-4
ISSN: 0031-6970
PubMed: 38347227
WoS: 001159759300002
Scopus: 2-s2.0-85184889713
Институција/група
PharmacyTY - JOUR AU - Škorić, Biljana AU - Jovanović, Marija AU - Kuzmanović, Miloš AU - Miljković, Branislava AU - Vučićević, Katarina PY - 2024 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5583 AB - Purpose: The aim of the present study was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) and to describe the influence of variability factors. Methods: The study included 50 patients of both sexes (aged 1–18 years) who received 3 or 5 g/m2 of HDMTX. A nonlinear mixed effect modeling approach was applied for data analysis. Parameter estimation was performed by first-order conditional estimation method with interaction (FOCEI), whereas stepwise covariate modeling was used to assess variability factors. Results: The final model is a two-compartment model that incorporates the effect of body surface area and the influence of hemoglobin and serum creatinine on MTX clearance (CL). Population pharmacokinetic values for a typical subject were estimated at 5.75 L/h/m2 for clearance (CL), 21.3 L/m2 for volume of the central compartment (V1), 8.2 L/m2 for volume of the peripheral compartment (V2), and 0.087 L/h/m2 for intercompartmental clearance (Q). According to the final model, MTX CL decreases with increasing serum creatinine, whereas a positive effect was captured for hemoglobin. A difference of almost 32% in MTX CL was observed among patients’ hemoglobin values reported in the study. Conclusion: The developed population pharmacokinetic model can contribute to the therapy optimization during HDMTX in pediatric patients with ALL and NHL. In addition to renal function and body weight, it describes the influence of hemoglobin on CL, allowing better understanding of its contribution to the disposition of HDMTX. PB - Springer Science and Business Media Deutschland GmbH T2 - European Journal of Clinical Pharmacology T1 - Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies DO - 10.1007/s00228-024-03642-4 ER -
@article{ author = "Škorić, Biljana and Jovanović, Marija and Kuzmanović, Miloš and Miljković, Branislava and Vučićević, Katarina", year = "2024", abstract = "Purpose: The aim of the present study was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) and to describe the influence of variability factors. Methods: The study included 50 patients of both sexes (aged 1–18 years) who received 3 or 5 g/m2 of HDMTX. A nonlinear mixed effect modeling approach was applied for data analysis. Parameter estimation was performed by first-order conditional estimation method with interaction (FOCEI), whereas stepwise covariate modeling was used to assess variability factors. Results: The final model is a two-compartment model that incorporates the effect of body surface area and the influence of hemoglobin and serum creatinine on MTX clearance (CL). Population pharmacokinetic values for a typical subject were estimated at 5.75 L/h/m2 for clearance (CL), 21.3 L/m2 for volume of the central compartment (V1), 8.2 L/m2 for volume of the peripheral compartment (V2), and 0.087 L/h/m2 for intercompartmental clearance (Q). According to the final model, MTX CL decreases with increasing serum creatinine, whereas a positive effect was captured for hemoglobin. A difference of almost 32% in MTX CL was observed among patients’ hemoglobin values reported in the study. Conclusion: The developed population pharmacokinetic model can contribute to the therapy optimization during HDMTX in pediatric patients with ALL and NHL. In addition to renal function and body weight, it describes the influence of hemoglobin on CL, allowing better understanding of its contribution to the disposition of HDMTX.", publisher = "Springer Science and Business Media Deutschland GmbH", journal = "European Journal of Clinical Pharmacology", title = "Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies", doi = "10.1007/s00228-024-03642-4" }
Škorić, B., Jovanović, M., Kuzmanović, M., Miljković, B.,& Vučićević, K.. (2024). Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies. in European Journal of Clinical Pharmacology Springer Science and Business Media Deutschland GmbH.. https://doi.org/10.1007/s00228-024-03642-4
Škorić B, Jovanović M, Kuzmanović M, Miljković B, Vučićević K. Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies. in European Journal of Clinical Pharmacology. 2024;. doi:10.1007/s00228-024-03642-4 .
Škorić, Biljana, Jovanović, Marija, Kuzmanović, Miloš, Miljković, Branislava, Vučićević, Katarina, "Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies" in European Journal of Clinical Pharmacology (2024), https://doi.org/10.1007/s00228-024-03642-4 . .