Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Immunosuppressants in Allogeneic Hematopoietic Cell Transplantation: Part II

Clin Pharmacokinet. 2016 May;55(5):551-93. doi: 10.1007/s40262-015-0340-9.

Abstract

Part I of this article included a pertinent review of allogeneic hematopoietic cell transplantation (alloHCT), the role of postgraft immunosuppression in alloHCT, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of the calcineurin inhibitors and methotrexate. In this article (Part II), we review the pharmacokinetics, pharmacodynamics, and pharmacogenomics of mycophenolic acid (MPA), sirolimus, and the antithymocyte globulins (ATG). We then discuss target concentration intervention (TCI) of these postgraft immunosuppressants in alloHCT patients, with a focus on current evidence for TCI and on how TCI may improve clinical management in these patients. Currently, TCI using trough concentrations is conducted for sirolimus in alloHCT patients. Several studies demonstrate that MPA plasma exposure is associated with clinical outcomes, with an increasing number of alloHCT patients needing TCI of MPA. Compared with MPA, there are fewer pharmacokinetic/dynamic studies of rabbit ATG and horse ATG in alloHCT patients. Future pharmacokinetic/dynamic research of postgraft immunosuppressants should include '-omics'-based tools: pharmacogenomics may be used to gain an improved understanding of the covariates influencing pharmacokinetics as well as proteomics and metabolomics as novel methods to elucidate pharmacodynamic responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antilymphocyte Serum / pharmacology
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / pharmacology*
  • Mycophenolic Acid / pharmacokinetics
  • Mycophenolic Acid / pharmacology
  • Pharmacogenetics
  • Sirolimus / pharmacokinetics
  • Sirolimus / pharmacology

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Sirolimus