title: The compelling case for therapeutic drug monitoring of mycophenolate mofetil therapy.
abstract: We have reviewed current evidence on the therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) in relationship to drug efficacy and safety. The relationship between actual MPA exposure and mycophenolate mofetil (MMF) dose has been shown to be weak in children and adolescents. The TDM of MPA exposure should ideally be performed using full pharmacokinetic profiles or limited sampling strategies. Recent evidence has provided some rationale for using the post-dose trough level as a single measure. In terms of short-term efficacy, there is strong evidence that a MPA area under the time-concentration curve of >30 mg × h/L reduces acute rejection episodes early after renal transplantation, and there is evolving evidence that aiming for the same exposure over the long term may be a viable strategy to reduce the formation of donor-specific antibodies. Strong evidence also supports the existence of important drug interactions and age/developmental dependent differences in drug metabolism that may necessitate the need for TDM of MMF therapy. Based on these findings and given the substantial inter- and intra-patient variability of MPA exposure, it would appear that MMF therapy should be subject to TDM to avoid over- and under-dosing. This may be a viable strategy to reduce treatment-emergent adverse events and to increase the effective pediatric transplant survival rates.
authors.affiliation: Department of Pediatrics, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5 W9, Canada. guido.filler@lhsc.on.ca.|Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, N5A 5A5, Canada. guido.filler@lhsc.on.ca.|Department of Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5 W9, Canada. guido.filler@lhsc.on.ca.|Department of Pediatrics, Children's Hospital, London Health Science Centre, Western University, 800 Commissioners Road East, London, ON, N6A 5 W9, Canada. guido.filler@lhsc.on.ca.
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
authors.affiliation: Department of Pediatrics, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5 W9, Canada.|Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico.|Laboratorio de Investigacion en Nefrologia, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico.
authors.forename: Ana Catalina
authors.initials: AC
authors.lastname: Alvarez-Elías
authors.affiliation: Department of Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5 W9, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: McIntyre
authors.affiliation: Laboratorio de Investigacion en Nefrologia, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico.|Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, Mexico.
authors.forename: Mara
authors.initials: M
authors.lastname: Medeiros
mesh_terms: D000293:Adolescent; D002648:Child; D016903:Drug Monitoring; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D009173:Mycophenolic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid
keywords: Intra-patient variability; Mycophenolate mofetil; Mycophenolic acid; Ontogeny; Therapeutic drug monitoring; Trough level