Artículo
Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK
Autor/es | Zazo Gómez, Hinojal
Lagarejos González, Eduardo Prado Velasco, Manuel Augusto Sánchez Herrero, Sergio Serna Pérez, Jenifer Rueda Ferreiro, Almudena Martín Suárez, Ana Calvo Hernández, María Victoria Pérez Blanco, Jonás Samuel Martínez Lanao, José |
Departamento | Universidad de Sevilla. Departamento de Ingeniería Gráfica |
Fecha de publicación | 2022 |
Fecha de depósito | 2023-05-08 |
Publicado en |
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Resumen | Each year, infections caused around the 25% of neonatal deaths. Early empirical treatments help to reduce this mortality, although optimized dosing regimens are still lacking. The aims were to develop and validate a ... Each year, infections caused around the 25% of neonatal deaths. Early empirical treatments help to reduce this mortality, although optimized dosing regimens are still lacking. The aims were to develop and validate a gentamicin physiologically-based pharmacokinetic (PBPK) model and then potentially explore dosing regimens in neonates using pharmacokinetic and pharmacodynamic criteria. The PBPK model developed consisted of 2 flowlimited tissues: kidney and other tissues. It has been implemented on a new tool called PhysPK, which allows structure reusability and evolution as predictive engine in Model-Informed Precision Dosing (MIPD). Retrospective pharmacokinetic information based on serum levels data from 47 neonates with gestational age between 32 and 39 weeks and younger than one-week postnatal age were used for model validation. The minimal PBPK model developed adequately described the gentamicin serum concentration-time profile with an average fold error nearly 1. Extended interval gentamicin dosing regimens (6 mg/kg q36h and 6 mg/kg q48h for term and preterm neonates, respectively) showed efficacy higher than 99% with toxicity lower than 10% through Monte Carlo simulation evaluations. The gentamicin minimal PBPK model developed in PhysPK from literature information, and validated in preterm and term neonates, presents adequate predictive performance and could be useful for MIPD strategies in neonates. |
Cita | Zazo Gómez, H., Lagarejos González, E., Prado Velasco, M.A., Sánchez Herrero, S., Serna Pérez, J., Rueda Ferreiro, A.,...,Martínez Lanao, J. (2022). Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK. Frontiers in Pharmacology, 13 (977372). https://doi.org/10.3389/fphar.2022.977372. |
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