Monitoring mycophenolic acid.
The immunosuppressive agent mycophenolate mofetil is a prodrug for the active compound mycophenolic acid. Following organ transplantation, it is used mostly in combination with other immunosuppressive drugs, but it has also been used as primary therapy. Although in the pivotal clinical studies the drug was given in fixed doses, there has been substantial interest in the measurement of mycophenolic acid in plasma as a guide to optimizing therapy. Data have emerged which indicate that the metabolism of the compound is more complex than was originally thought and that variability in exposure to the drug, assessed by area under the time-concentration curve, is an important determinant of efficacy. This article highlights basic pharmacokinetic and pharmacodynamic data for mycophenolic acid, which underlie the rationale for its measurement. These data are then set in the context of providing a routine service for the measurement of the drug with either of the analytical techniques currently available--immunoassay or high-performance liquid chromatography. There are a number of issues regarding the clinical interpretation of mycophenolic acid measurements which are yet to be resolved. Centres contemplating the introduction of such a service will need to keep abreast of a rapidly evolving literature.
Holt
David W
DW
Analytical Unit, St. George's Hospital Medical School, London, UK. d.holt@sghms.ac.uk
D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D006801:Humans; D007118:Immunoassay; D016030:Kidney Transplantation; D016040:Lung Transplantation; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000032:analysis; D013997:Time Factors
D011355:Prodrugs; D009173:Mycophenolic Acid