Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation.
Int J Clin Pharmacol Ther
; 53(1): 75-83, 2015 Jan.
Article
en En
| MEDLINE
| ID: mdl-25207550
OBJECTIVE: The purpose of this study was to describe the population pharmacokinetics (PK) of tacrolimus (TAC) in 52 Chinese pediatric patients early after liver transplantation. METHODS: Details of drug dose, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data from the first day after surgery. A total of 488 concentration data were obtained and analyzed by a nonlinear mixed-effect modeling (NONMEM) method. A number of demographic and clinical variables were tested for their influence on TAC PK parameters. RESULTS: The PK of TAC were best described by a one-compartment model with first-order absorption and elimination. Apparent clearance (CL/F) and apparent volumes of distribution (V/F) in final population model were 5.72 L/h and 131 L, respectively. The absorption rate constant (Ka) was fixed in 4.48 h-1. The inter-individual variabilities in CL/F and V/F were 13.5% and 78.1%. In the final analysis performed in all 52 patients, the post-operation day (POD) and alanine aminotransferase (ALT) influenced TAC CL/F and V/F, and total protein (TP) was the only covariate retained on V/F. CONCLUSION: A population PK model of TAC was developed in Chinese pediatric patients early after liver transplantation. It identified significant relationships between the PK of TAC and the characteristics of the patients. POD, ALT, and TP were identified as the main factors influencing the PK of TAC. The developed model could be useful to optimize individual pediatric TAC dosing regimen in routine clinical practice.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trasplante de Hígado
/
Tacrolimus
/
Rechazo de Injerto
/
Inmunosupresores
/
Modelos Biológicos
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
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Infant
/
Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
Int J Clin Pharmacol Ther
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2015
Tipo del documento:
Article
Pais de publicación:
Alemania