Limited sampling strategy for estimating exposure to mycophenolic acid in patients with autoimmune disease / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish limited sampling strategies for the estimation of exposure (AUC) to mycophenolic acid (MPA) in patients with autoimmune disease (AID). METHODS: The 24 AID patients were treated with MMF 0.75 g q12 h to steady state. Serum MPA concentrations were measured at pre-dose, 0.5,1,1.5,2,4,6,8 and 12 h after dosage and MPA AUC0-12 h were caculated with the trapezoidal rule. The resulted data were randomly devided into index set and validation set. Multiple liner regression analysis of the index set was used to determine the 1 to 4 sampling estimation models and the models were validated in the validation set. The prediction bias and precision combining clinical feasibility were used to choose the final models. RESULTS: The 1-point model based on the simple measurement of c12 h produced acceptable prediction for MPA AUC0-12 h, in which, r was 0.957, the prediction bias and imprecision were repectively-3.93 and 11.93, both <15%; 4-point model based on 0.5,1.5,6,8 h or 1.5,6,8,12 h sampling times were fitted to MPA AUC0-12 h, with highest correlation coefficients of 0.996, and prediction errors between ±15% for 9 patients; other 2 or 3-point models resulted somewhere in-between prediction performance. CONCLUSION: Considering the clinical feasibility, the accurate 4-point model AUC=3.19+0.49c0.5 h+1.76c1.5 h+2.95c6 h+5.46c8 h is applicable to MPA AUC monitoring in AID inpatients after morning dose; the simple 1-point model AUC=10.82+13.37c12 h is a good choice for AID outpatients after last-night dose. Bland-Altman analysis reveals that both the two models could effectively predict MPA AUC in Chinese adult AID patients receiving MMF concomitant methylprednisolone therapy.