Population pharmacokinetics of mycophenolate in patients treated for interstitial lung disease (EVER‐ILD study)

Author:

Xu Yan‐Min1,Ternant David23ORCID,Reynaud‐Gaubert Martine4,Bejan‐Angoulvant Théodora23,Marchand‐Adam Sylvain15

Affiliation:

1. CHRU de Tours Service de Pneumologie et d'Explorations Fonctionnelles Respiratoires Tours France

2. INSERM UMR1327 ISCHEMIA Université de Tours Tours France

3. CHRU de Tours Service de Pharmacologie Médicale Tours France

4. Service de Pneumologie, Centre de Compétences des Maladies Pulmonaires Rares, APHM, CHU Nord Aix Marseille Université Marseille France

5. Centre d'Etude des Pathologies Respiratoires (CEPR) INSERM U1100 Faculté de Médecine Université de Tours Tours France

Abstract

AbstractBackgroundMycophenolate 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.MethodsConcentrations 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.ResultsThe 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 AUC12 = 52.5 mg.h/L in median (interquartile range: 42.2–58.0 mg.h/L).ConclusionThis 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.

Publisher

Wiley

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