Pharmacokinetics of Mycophenolate Mofetil Metabolites in Older Patients on the Seventh Day After Renal Transplantation.

Background: Currently, immunosuppression schemes are age-independent; however, physiological changes may alter drugs' pharmacokinetics in the older population. We compared mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) pharmacokinetics among patients aged <60 and >60 years on the seventh day after renal transplantation.

Methods: We included 7 and 10 renal transplant recipients, aged >60 and <60 years, respectively, treated with mycophenolate mofetil. MPA and MPAG concentrations were determined using the high-performance liquid chromatography method with ultraviolet detection (HPLC-UV). Noncompartmental pharmacokinetic analysis was performed.

Results: In patients aged >60 years, mean MPA and MPAG concentrations before the next dose and ratio of MPAG area under the concentration-time curve (AUC) to MPA AUC were higher by 1.6-fold, 1.4-fold, and 1.9-fold, respectively. Other MPAG concentrations appeared to be slightly higher (1.2- to 1.5-fold) in older patients. MPA apparent clearance was similar in both groups, whereas volume of distribution at steady state was slightly higher (1.6-fold) in patients aged >60 years. The variability of most MPA and some MPAG pharmacokinetics was greater in patients aged >60 years. The MPA AUC target was achieved in 40% and 14% of patients aged <60 and >60 years, respectively. The highest MPAG concentrations and AUC were observed for patients with the lowest glomerular filtration rate.

Conclusions: Higher variability of MPA and MPAG pharmacokinetic parameters, MPA AUC above the reference range, higher values of MPAG pharmacokinetics in patients with lower glomerular filtration rates, as well as lower proportion of patients achieving MPA targets all indicate the need for therapeutic drug monitoring in renal transplant recipients aged >60 years and to verify target MPA AUC for this population.