Creatinine- and cystatin C-based population pharmacokinetic models for predicting mycophenolic acid clearance in patients with autoimmune diseases

Selecting the right renal function equation is important for predicting mycophenolic acid (MPA) clearance and optimizing mycophenolate mofetil dosing in autoimmune disease patients, but the relative performance of creatinine- versus cystatin C-based equations was unclear. This retrospective study analyzed 176 plasma samples from 37 adult autoimmune disease patients to compare renal function equations within a population pharmacokinetic model built using Phoenix NLME. Creatinine clearance (via the Cockcroft-Gault equation) most effectively predicted MPA clearance, along with serum albumin, likely because creatinine and a major MPA metabolite share a tubular secretion elimination pathway that cystatin C does not capture. The findings support using creatinine-based equations for MPA dosing in adults with autoimmune disease, while noting cystatin C-based equations may still be preferable in pediatric or low-muscle-mass populations.