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Anticipating Leucovorin Rescue Therapy in Patients with Osteosarcoma through Methotrexate Population Pharmacokinetic Model.
Olivo, Laura Ben; de Oliveira Henz, Pricilla; Wermann, Sophia; Dias, Bruna Bernar; Porto, Gabriel Osorio; Pinhatti, Amanda Valle; Martins, Manoela Domingues; Gregianin, Lauro José; Costa, Teresa Dalla; de Araújo, Bibiana Verlindo.
Afiliação
  • Olivo LB; Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande do Sul, 2752 Ipiranga Ave., Santana, Porto Alegre 90610-000, RS, Brazil.
  • de Oliveira Henz P; Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande do Sul, 2752 Ipiranga Ave., Santana, Porto Alegre 90610-000, RS, Brazil.
  • Wermann S; Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande do Sul, 2752 Ipiranga Ave., Santana, Porto Alegre 90610-000, RS, Brazil.
  • Dias BB; Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande do Sul, 2752 Ipiranga Ave., Santana, Porto Alegre 90610-000, RS, Brazil.
  • Porto GO; Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande do Sul, 2752 Ipiranga Ave., Santana, Porto Alegre 90610-000, RS, Brazil.
  • Pinhatti AV; Medical Sciences Graduate Program, Federal University of Rio Grande do Sul, Porto Alegre 90610-000, RS, Brazil.
  • Martins MD; Faculty of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre 90610-000, RS, Brazil.
  • Gregianin LJ; Faculty of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre 90610-000, RS, Brazil.
  • Costa TD; Pediatric Oncology Service, Hospital de Clínicas de Porto Alegre, Department of Pediatrics, Federal University of Rio Grande do Sul, Porto Alegre 90610-000, RS, Brazil.
  • de Araújo BV; Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande do Sul, 2752 Ipiranga Ave., Santana, Porto Alegre 90610-000, RS, Brazil.
Pharmaceutics ; 16(9)2024 Sep 06.
Article em En | MEDLINE | ID: mdl-39339216
ABSTRACT
Methotrexate (MTX), which presents high inter-individual variability, is part of the Brazilian Osteosarcoma Treatment Group (BOTG) protocol. This work aimed to develop a MTX population pharmacokinetic model (POPPK) for Brazilian children with osteosarcoma (OS) following the BOTG protocol to guide rescue therapy and avoid toxicity. The model was developed in NONMEM 7.4 (Icon®) using retrospective sparse data from MTX therapeutic drug monitoring of children attending a southern Brazilian public reference hospital. Data were described by a two-compartment model using 216 MTX cycles from 32 patients (5-18 y.o.) with OS who received 12 g/m2 dose/cycle. To explain inter-individual and inter-occasion variability in clearance and peripheral volume, covariates from demographic and biochemical data were evaluated. Serum creatinine was a significant covariate of MTX clearance (14.8 L/h), and the body surface area (BSA) was significant for central compartment volume (82.5 L). Inter-compartmental clearance and volume of peripheral compartment were 0.178 L/h and 5.72 L, respectively. The model adequately describes MTX exposure in Brazilian children with OS. Successful simulations were performed to predict MTX concentrations in pediatric patients above five years old with acute kidney injury and anticipate rescue therapy adjustments.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Pharmaceutics Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Pharmaceutics Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça