Open AccessPersonalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology
Author(s) -
Stein Bergan,
Mercè Brunet,
Dennis A. Hesselink,
Kamisha L. Johnson-Davis,
Paweł K. Kunicki,
F. Lemaître,
Pierre Marquet,
Mariadelfina Molinaro,
Ofelia Noceti,
Smita Pattanaik,
Tomasz Pawiński,
Christoph Seger,
Maria Shipkova,
Jesse J. Swen,
Teun van Gelder,
Raman Venkataramanan,
Eberhard Wieland,
JeanBaptiste Woillard,
Tom C. Zwart,
M.J. Barten,
Klemens Budde,
MajaTheresa Dieterlen,
Laure Elens,
Vincent Haufroid,
Satohiro Masuda,
Olga Millán,
Tomoyuki Mizuno,
Dirk Jan A. R. Moes,
Michael Oellerich,
Nicolas Picard,
Linda Salzmann,
Burkhard Tönshoff,
Ron H. N. van Schaik,
Nils Tore Vethe,
Alexander A. Vinks,
Pierre Wallemacq,
Anders Åsberg,
Loralie J. Langman
Publication year - 2021
Publication title -
therapeutic drug monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.649
H-Index - 93
eISSN - 1536-3694
pISSN - 0163-4356
DOI - 10.1097/ftd.0000000000000871
Subject(s) - medicine , therapeutic drug monitoring , dosing , regulatory science , mycophenolic acid , intensive care medicine , personalized medicine , medline , drug , drug development , medical physics , pharmacology , bioinformatics , transplantation , pathology , political science , law , biology
When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.