Using established immunosuppressant therapy effectively: lessons from the measurement of mycophenolic acid plasma concentrations.
Getting the most effective use of immunosuppressant medications in transplant patients continues to be a major challenge in clinical practice. This need applies to established immunosuppressants just as it does to new agents. In this review this principle is illustrated for mycophenolic acid, the active metabolite of mycophenolate mofetil, the most commonly used immunosuppressant, in various combinations with other immunosuppressants, in current clinical practice. Defining, as rigorously as possible, the requirements for effective therapeutic monitoring of MPA is an important goal given all of the changes in immunosuppressive drug regimens. This review will focus on the major factors known to influence MPA clearance including: UDP-glucuronyltransferases, enterohepatic circulation, MPA free fraction, the effect of time posttransplantation, concomitant administration of immunosuppressant drugs. The significant variability of MPA pharmacokinetics and the need to deepen our understanding of the influence of these factors on MPA clearance are strong reasons why additional clinical trials are needed to define best practice therapeutic drug monitoring of this drug.
Shaw
Leslie M
LM
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA. shawlmj@mail.med.upenn.edu
Nawrocki
Arthur
A
Korecka
Magdalena
M
Solari
Sandra
S
Kang
Juseop
J
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D015331:Cohort Studies; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D004764:Enterohepatic Circulation; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D014181:Transplantation Immunology
D000305:Adrenal Cortex Hormones; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D014453:Glucuronosyltransferase; D009173:Mycophenolic Acid; D020123:Sirolimus