title: Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Immunosuppressants in Allogeneic Hematopoietic Cell Transplantation: Part II.
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.
authors.affiliation: Department of Pharmacy, University of Washington, Box 357630, Seattle, WA, 98195, USA. jmccune@u.washington.edu.|Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA, 98195, USA. jmccune@u.washington.edu.|Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. jmccune@u.washington.edu.
authors.forename: Jeannine S
authors.initials: JS
authors.lastname: McCune
authors.affiliation: Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA, 98195, USA.
authors.forename: Meagan J
authors.initials: MJ
authors.lastname: Bemer
authors.affiliation: Department of Clinical Pharmacy, University of California San Francisco, San Francisco, CA, 94131, USA.
authors.forename: Janel
authors.initials: J
authors.lastname: Long-Boyle
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009173:Mycophenolic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D010597:Pharmacogenetics; D020123:Sirolimus / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus