Are in clinical practice measurements of concentrations and the calculation of mycophenolate mofetil pharmacokinetic parameters needed for optimizing therapy in patients with renal diseases or kidney transplantation?

Abstract

Modern pharmacotherapy requires an individual approach to patients, taking into account changes in pharmacokinetics in pathological states and between-subject variability. This procedure is of particular importance in immunosuppressive drug therapy. In recent years, the attention has been paid to the usefulness of calculating the kinetic parameters of the drug in the optimization of the immunosuppressive treatment. To assess the possibility of using mycophenolic acid (MPA) concentration measurements in order to optimize pharmacotherapy in patients with kidney diseases or after kidney transplantation. The study included 103 patients with renal diseases (group 1) and after kidney transplantation (group 2), treated at the Department of Nephrology and Transplantation Medicine at the University Clinical Hospital, Wrocław, Poland. The concentrations of MPA were measured using Enzyme Multiplied Immunoassay Technique (EMIT®) method. A total of 193 pharmacokinetic profiles were performed. The median of initial (C0) concentration for all patients was 2.09 mg/L, in group 1 - 2.06 mg/L and in group 2 - 2.11 mg/L. The median concentration at 30 min after drug administration (C30) was 11.72 mg/L in the whole study group, in group 1 - 11.52 mg/L and in group 2 - 12.72 mg/L. The median concentration at 120 min after the drug administration (C120) was 4.73 mg/L, 4.45 mg/L and 5.57 mg/L, respectively. The median area under the curve from C0 to C120 (AUC)0-120 was 15.77 h × mg/L for the entire study group, in group 1 - 15.46 h × mg/L and in group 2 - 16.78 h × mg/L. Using the Spearman's rank correlation coefficient for both groups, statistically significant (p < 0.05) correlations were found between 1) C0 and C30, 2) C0 and C120, 3) C0 and AUC0-120, 4) C0 and the daily dose, 5) C30 and AUC0-120, and 6) C30 and the morning dose. There were also statistically significant correlations between C120 and AUC0-120. Moreover, in group 1, a statistically significant correlation (p < 0.05) was found between 1) C120 and the daily dose, 2) C120 and albumin, 3) C120 and C30, and 4) C120 and AUC0-120. In the group 2, a statistically significant correlation was found between C120 and the morning dose. Measurements of MPA concentrations are useful for optimizing immunosuppression in patients requiring an individualized treatment.