Analyse pharmacocinétique de la population de tacrolimus chez les patients atteints de myasthénie grave en Chine

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Analyse pharmacocinétique de la population de tacrolimus chez les patients atteints de myasthénie grave en Chine

Message par Pboulanger » 02 juin 2017 12:15


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Population pharmacokinetic analysis of tacrolimus in Chinese myasthenia gravis patients.
Chen YS1, Liu ZQ2, Chen R3,4, Wang L5, Huang L2, Zhu X6, Zhou TY3,4, Lu W3,4, Ma P2.

PMID: 28552913
DOI: 10.1038/aps.2016.174


The importance of tacrolimus in the treatment of myasthenia gravis (MG) as a substitute for corticosteroid-dependent immunosuppressive therapy is increasing. Thus far, however, no population pharmacokinetic (PopPK) analysis of tacrolimus in treating MG patients has been published.

This article aimed to construct a PopPK model of tacrolimus for Chinese MG patients with the goal of improving its performance in MG treatment.
A total of 253 trough concentration records were obtained from 83 Chinese MG patients.

The effects of demographics, lifestyle and health status, biochemical test data, disease progression and treatment-related information (including co-administered medications) as covariates on the various parameters were investigated.

The covariate selection was based on biological plausibility, clinical significance, statistical significance and reduction in inter-individual variability (IIV). Bootstrap and normalized prediction distribution error (NPDE) analysis were performed to validate the final model.
A one-compartment PopPK model with first-order elimination and a fixed absorption phase was constructed.

The estimated apparent oral clearance (CL/F) and apparent oral volume of distribution (V/F) were 3.6 L/h and 1700 L, respectively, in the MG patients. Hematocrit and blood urea nitrogen were identified as two covariates that significantly influenced the CL/F.

Immunoglobulin treatment (PRO) also had the potential to influence V/F, which was consistent with the clinical observations and the high protein-binding property of tacrolimus. Other covariates including age, weight, gender and co-administered medications had no obvious influence on CL/F or V/F.

The first PopPK model of tacrolimus in MG patients was established.

The identified covariates were of biological plausibility and clinical importance to help individualize the dosing schedule in MG patients.



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