Population pharmacokinetics of everolimus in renal transplant recipients receiving long-term multiple immunosuppressive therapy.
Drug Metab Pharmacokinet
; 56: 101009, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38547661
ABSTRACT
Everolimus is used for immunosuppression after renal transplantation. This study aimed to develop a population pharmacokinetic (PopPK) model of everolimus using therapeutic drug monitoring (TDM) data of patients under long-term multiple immunosuppressive therapy, including tacrolimus. To develop the model, 185 renal transplant recipients with 3358 everolimus blood concentrations during a median postoperative period of 35.3 months were included. The PopPK model is described as a one-compartment model with first-order absorption. The population mean of apparent clearance is 8.92 L/h (relative standard error = 3.6%), and this negatively correlated with the dose-normalized concentration (C/D) of tacrolimus and hematocrit value, and positively correlated with a daily dose of everolimus (i.e. TDM effect). The usefulness of dose adjustment using the final popPK model was assessed by a simulation study. The ratio of the first trough measurement within the therapeutic range of 3-8 ng/mL increased from 69.8% in the original dose to 87.9% in the individual dose calculated by the final PopPK model. The tacrolimus C/D ratio before initiating everolimus therapy and the hematocrit value were useful to estimate the initial dose of everolimus and can improve the safety and effectiveness of immunosuppressive therapy involving everolimus.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante de Rim
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Monitoramento de Medicamentos
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Everolimo
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Imunossupressores
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article