Development of population PK model with enterohepatic circulation for mycophenolic acid in patients with childhood‐onset systemic lupus erythematosus

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

AIM

This study aimed to develop a population pharmacokinetic (PK) enterohepatic recycling model for MPA in patients with childhood‐onset systemic lupus erythematosus (cSLE).

METHODS

MPA concentration–time data were from outpatients on stable oral mycophenolate mofetil (MMF) and collected under fasting conditions, with standardized meals (1 and 4 h post‐dose). Sampling times were pre‐dose, 20, 40 min, 1, 1.5, 2, 3, 4, 6 and 9 h, post dose. The population PK analysis simultaneously modelled MPA and 7‐O‐MPA‐β‐glucuronide (MPAG) concentrations using nonlinear mixed effect modelling.

RESULTS

PK analysis included 186 MPA and MPAG concentrations (mg l^–1) from 19 patients. cSLE patients, age range 10–28 years, median 16.5 years were included. Mean ± SD disease duration was 3.8 ± 3.7 years. The final PK model included a gallbladder compartment for enterohepatic recycling and bile release time related to meal times, with first order absorption and single series of transit compartments. The PK estimates for MPA were CL₁/F 25.3 l h^–1, V₃/F 20.9 l, V₄/F 234 l and CL₂/F 19.8 l h^–1.

CONCLUSION

The final model fitted the complex processes of absorption and enterohepatic circulation (EHC) in those treated with MMF for cSLE and could be applied in Bayesian dose optimization algorithms.

DOI: 10.1111/j.1365-2125.2011.04140.x

View this article

• Full article (html)
• Enhanced article (html)
• PDF
• References