Pharmacokinetics and concentration-control investigations of mycophenolic acid in adults after transplantation

Leslie M. Shaw, Bruce Kaplan, David DeNofrio, Magdalena Korecka, Kenneth L. Brayman

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Data have emerged that provide the scientific basis for therapeutic drug monitoring of mycophenolic acid (MPA) in transplant patients receiving mycophenolate mofetil (MMF), the parent drug, in combination with other immunosuppressive agents. There is a significant relationship between the dose-interval MPA AUC and risk for acute rejection based on retrospective investigations in renal and heart transplant patients and on prospective investigations in renal transplant patients. The MPA dose-interval AUC varies naturally by more than 10-fold in renal and heart transplant patients. Other significant sources of pharmacokinetic variability for MPA include the effects of concomitant medications, and the effects of disease states such as renal dysfunction and liver disease on the steady state MPA AUC. Individualized MMF dose evaluation, guided by MPA plasma concentrations, is becoming the standard of practice at a growing number of transplant centers worldwide because of these factors and because of the need to closely evaluate the immunosuppression afforded by MPA when a change in the immunosuppression regimen in stable transplant patients is planned. Investigations of therapeutic drug monitoring strategies with an emphasis on identifying an optimal abbreviated sampling strategy for MPA AUC estimation are ongoing. Based on the concentration-outcome studies and experience at the authors' institutions and other centers, the authors propose a set of therapeutic drug monitoring guidelines for MPA in stable renal and heart transplant patients for the immediate (first 3 months posttransplant) and maintenance (>3 months) periods. When MPA binding to human serum albumin is altered, as occurs in patients with significant renal dysfunction, liver disease, or a substantial reduction in human serum albumin concentration, the possibility of increased MPA free fraction and free concentration will need to be taken into account in the interpretation of MPA total concentrations.

Original languageEnglish (US)
Pages (from-to)14-19
Number of pages6
JournalTherapeutic Drug Monitoring
Volume22
Issue number1
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Mycophenolic Acid
Pharmacokinetics
Transplantation
Transplants
Kidney
Area Under Curve
Drug Monitoring
Serum Albumin
Pharmaceutical Preparations
Liver
Immunosuppression
Liver Diseases
Monitoring
Personal Autonomy
Drug Combinations
Immunosuppressive Agents

Keywords

  • Mycophenolic acid
  • Renal and heart transplants
  • Risk of rejection

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Pharmacology
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health

Cite this

Pharmacokinetics and concentration-control investigations of mycophenolic acid in adults after transplantation. / Shaw, Leslie M.; Kaplan, Bruce; DeNofrio, David; Korecka, Magdalena; Brayman, Kenneth L.

In: Therapeutic Drug Monitoring, Vol. 22, No. 1, 2000, p. 14-19.

Research output: Contribution to journalArticle

Shaw, Leslie M. ; Kaplan, Bruce ; DeNofrio, David ; Korecka, Magdalena ; Brayman, Kenneth L. / Pharmacokinetics and concentration-control investigations of mycophenolic acid in adults after transplantation. In: Therapeutic Drug Monitoring. 2000 ; Vol. 22, No. 1. pp. 14-19.
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