Evalutation of mycophenolic acid systemic exposure by limited sampling strategy in kidney transplant recipients receiving enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine.

Background: Enteric-coated mycophenolate sodium (EC-MPS) and mycophenolate mofetil (MMF) are prodrugs of mycophenolic acid (MPA). Although many patients still receive MMF as an inosine monophosphate dehydrogenase inhibitor, EC-MPS could be considered a reliable alternative to MMF in the immunosuppressive protocols of kidney transplant recipients. MPA shows high pharmacokinetic variability and consequently a 12-h area under the curve (AUC(0-12)) should be used to guide the therapeutic dosage. However, patient compliance and economic costs make MPA AUC(0-12) an unpractical approach. Limited sampling strategies or predictive systemic drug exposure equation models based on limited sampling times are available only for MMF but lack for EC-MPS.

Methods: The present study enrolled 26 kidney transplant recipients receiving EC-MPS as part of their immunosuppressive therapy. Twenty-six full MPA AUC(0-12) were performed. By using multiple stepwise regression analysis, we obtained several predictive equations of MPA systemic exposure in this group of patients. The value of the selected equations was tested in a subsequently enrolled group of 26 kidney transplant recipients.

Results: The best equations obtained in the first group of patients were the following: 22.906 + 3.880·C(0) + 1.117·C(1) + 7.527·C(8) (r = 0.901) and 35.064 +3.784·C(0) + 1.002·C(1) + 1.192·C(2) (r = 0.846). These equation models showed an optimal agreement between the full AUCs and estimated AUCs by using the validation group of patients.

Conclusions: Limited sampling strategies are useful for MPA AUC(0-12) estimation in patients receiving EC-MPS and cyclosporine. The choice of one or the other equation model depends on the pharmacokinetic characteristics of the patients, in particular the potential presence of enterohepatic recirculation.