Population pharmacokinetics of mycophenolic acid in adult kidney transplant patients under prednisone and tacrolimus regimen.
Eur J Pharm Sci
; 150: 105370, 2020 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-32387086
Mycophenolate mofetil (MMF) is typically used in combination with prednisone and tacrolimus to avoid graft rejection in kidney transplant patients. The aim of this study was to develop and validate a population pharmacokinetic model of mycophenolic acid (MPA) in kidney transplant patients to investigate the influence of clinical and genetic covariates and to propose a dosage regimen based on the final model. Adult kidney transplant patients (>18 years old) receiving combination of MMF, prednisone and tacrolimus regimen were included. The population pharmacokinetic model was built using a two-compartment model and First Order Conditional Estimation method with Interaction (FOCEI though NONMEM v.7.4.). A total of 343 MPA concentrations at steady state from 77 kidney transplant patients were included in the analysis. MPA CL/F, V1/F, Q/F, V2/F, and Ka were 12.4 L/h, 45.6 L, 29.9 L/h, 658 L, and 1.67 h-1, respectively. It was found that CL/F increases with serum creatinine and uric acid levels and V1/F is modified by blood urea nitrogen and the UGT1A9 genotype. In the final model the interindividual variabilities associated to CL/F and V1/F were 56.5% and 105.8%, respectively. The residual variability was 41.8%. Evaluation by bootstrapping showed that the final model was stable. The predictive performance was evaluated by goodness-of-fit plots and visual predictive check. Dosage regimens for MMF were proposed based on the final model and would be appropriate for a prospective evaluation. In conclusion, it was built a population pharmacokinetic model for MPA in kidney transplant patients, which include clinical and genetic covariates.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trasplante de Riñón
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Inmunosupresores
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Modelos Biológicos
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Ácido Micofenólico
Tipo de estudio:
Observational_studies
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Prognostic_studies
Límite:
Adolescent
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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
Revista:
Eur J Pharm Sci
Asunto de la revista:
FARMACIA
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FARMACOLOGIA
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QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
México
Pais de publicación:
Países Bajos