Pharmacokinetics of Enteric-Coated Mycophenolate Sodium Metabolites in Patients Over 60 Years Old Within the First Year After Renal Transplantation

Abstract

ObjectiveIt is still unclear whether mycophenolic acid (MPA) doses should be adjusted for older patients. Therefore, we compared the pharmacokinetics of MPA, mycophenolic acid glucuronide (MPAG), and free MPA (fMPA) between older and younger renal transplant recipients. MethodsWe included 12 patients <60 years and 6 patients >60 years within the first year after renal transplantation, who were receiving enteric-coated mycophenolate sodium, tacrolimus, and steroids. Blood samples were collected up to 12 hours after drug administration. ResultsMPA and fMPA pharmacokinetics were similar for patients <60 and >60 years; however, the MPA area under the concentration-time curve from 0 to 12 hours (AUC0-12) was 1.2-fold lower in the older patients. MPAG pharmacokinetics were more than 1.5-fold higher in patients >60 years, which might be related to deteriorated renal function in older people. Moreover, the mean (MPAG AUC0-12)/(MPA AUC0-12) ratio was more than 2-fold higher in patients >60 years. The second maximal MPA concentration was more frequently observed in patients <60 years, although all patients received tacrolimus. The percentage of patients with MPA concentration before the next drug dose (Ctrough) and AUC0-12 within and below target was the same in both groups. All patients >60 years had MPA AUC0-12 >30 μg·h/mL within 22 to 114 days after transplantation. ConclusionsMPA therapeutic monitoring should be recommended in enteric-coated mycophenolate sodium--treated patients >60 years because MPA AUC0-12 exceeded the recommended value in half of the studied patients.