To what extent does the understanding of pharmacokinetics of mycophenolate mofetil influence its prescription.

Within a short period, we have witnessed a dramatic increase in the use of mycophenolate mofetil (MMF) in pediatric renal transplantation, with the drug often replacing azathioprine in combination with calcineurin inhibitor therapy. When the drug was introduced, the manufacturer considered therapeutic drug monitoring (TDM) unnecessary. However, TDM studies revealed substantial inter- and intra-individual variability and drug interactions. There is a substantial drug interaction between MMF and cyclosporine, and lower doses are required in combination with tacrolimus (~500-800 mg/m(2) per day) than with cyclosporine (~1,200 mg/m(2) per day). Patients with autoimmune disease require an intermediate dose when receiving no concomitant calcineurin inhibitor (~900 mg/m(2) per day). It has been possible to detect drug interactions and to minimize adverse events only with TDM. This is especially important with increasing use of combination therapies. Pharmacodynamic monitoring (measuring the biological response to a drug) coupled with pharmacokinetics allow optimization of drug dosing, with maximum efficacy and minimal toxicity. More work is required to establish specific target ranges with the various drug combinations--especially for the pediatric population.