Pharmacokinetics and Pharmacodynamics of Mycophenolic Acid: Different Formulations in Stable Renal Transplant Patients

Mycophenolic acid has gained widespread acceptance as the antimetabolite of choice in most of the immunosuppressive regimens, thanks to its selective action versus T and B cells. This drug is characterized by a narrow therapeutic index and a well-documented relationship between efficacy (in terms of acute rejection episodes) and exposure to mycophenolic acid (as AUC and C0). For these reasons, in the past years there has been an increased interest in the utility of monitoring mycophenolic acid concentration to optimize drug dosing. Currently, two prodrugs of mycophenolic acid are available, namely mycophenolate mofetil and the enteric-coated formulation of mycophenolate sodium. Both formulations provide comparable distribution, metabolism and excretion of mycophenolic acid. However, important differences in drug absorption have been reported. Some of them were expected, being related to the enteric-coating film of mycophenolate sodium that delayed the absorption of mycophenolic acid, resulting in higher Tmax values compared to those measured with mycophenolate mofetil. Nevertheless, a number of studies reported that the novel entericcoated formulation of mycophenolic acid produced aberrant and extremely variable pharmacokinetic profiles, characterized by multiple peaks of mycophenolic acid concentrations and high basal drug concentrations. According to these preliminary data, mycophenolate sodium and mycophenolate mofetil cannot be formally considered as bioequivalent. Moreover, the growing body of literature on the importance of therapeutic drug monitoring of mycophenolic acid poses concerns also on the “clinical equivalence” between the two formulations. It is, indeed, very unlikely that all the monitoring strategies applied in the past years for mycophenolate mofetil could be applied in patients given mycophenolate sodium, due to the erratic and extremely variable absorption of the novel formulation. As an additional limitation, no data are available yet on the factors that could potentially affect trends in transplant. 2008;2:51-61