Population pharmacokinetics of mycophenolate in patients treated for interstitial lung disease (EVER-ILD study).
Yan-Min Xu, David Ternant, Martine Reynaud-Gaubert, Th��odora Bejan-Angoulvant, Sylvain Marchand-Adam
Author Information
Yan-Min Xu: CHRU de Tours, Service de Pneumologie et d'Explorations Fonctionnelles Respiratoires, Tours, France.
David Ternant: INSERM UMR1327 ISCHEMIA, Universit�� de Tours, Tours, France. ORCID
Martine Reynaud-Gaubert: Service de Pneumologie, Centre de Comp��tences des Maladies Pulmonaires Rares, APHM, CHU Nord, Aix Marseille Universit��, Marseille, France.
Th��odora Bejan-Angoulvant: INSERM UMR1327 ISCHEMIA, Universit�� de Tours, Tours, France.
Sylvain Marchand-Adam: CHRU de Tours, Service de Pneumologie et d'Explorations Fonctionnelles Respiratoires, Tours, France.
BACKGROUND: Mycophenolate mofetil (MMF) has been used to treat interstitial lung disease (ILD), but mycophenolate (MPA) pharmacokinetics was not reported for this use. This ancillary study of the EVER-ILD protocol aimed at describing the pharmacokinetic variability of MPA using population modelling in ILD. METHODS: Concentrations of MPA were measured during an 8-h course for 27 ILD patients treated with 1000���mg MMF b.i.d. Absorption, distribution and elimination of MPA were described using population compartment models with first-order transfer and elimination rate constants, while accounting for both absorption peaks using gamma absorption models. RESULTS: The pharmacokinetics of MPA was best described using a two-compartment model and two gamma absorption models, model performances of this model were still similar to those of a one gamma absorption model. This pharmacokinetics seemed to be notably influenced by body weight, renal function and inflammatory status. The distribubtion value area under the concentration curve between two administrations of MMF was AUC���=���52.5 mg.h/L in median (interquartile range: 42.2-58.0 mg.h/L). CONCLUSION: This is the first study reporting MPA pharmacokinetics in ILD. This pharmacokinetics appears to be similar to other indications and should be further investigated in future studies.
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