title: Opportunity to monitor immunosuppressive drugs in peripheral blood mononuclear cells: where are we and where are we going?
abstract: Immunosuppressive (IS) drugs are now widely used as preventive treatments of allograft rejection in transplantation. Therapeutic drug monitoring (TDM) using trough whole blood concentrations is usually warranted and therapeutic range is recommended to ensure efficacy and prevent toxicity from these drugs. This intensive TDM reduces acute graft rejection but despite this management, the acute rejection rate still remains high in the first two years post-transplantation and few improvements have been made recently to reduce this rate. Moreover, in some patients, acute rejections occur despite adequate trough whole blood IS concentrations. Thus, other ways to monitor immunosuppressive drug effects have to be investigated. As lymphocyte cells are the site of action of IS drugs and so the effect compartment of the drug, monitoring IS drugs in lymphocytes, or for practical reasons in peripheral blood mononuclear cells (PBMC), could be more relevant than standard TDM. The aim of this paper is to review the recent work conducted on the advantages of monitoring IS drugs in PBMC, particularly for calcineurin inhibitors and mammalian target of rapamycin (m-TOR) inhibitors, from an analytical point of view as well as a clinical point of view.
authors.affiliation: Rennes University Hospital, Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes, France. florian.lemaitre@chu-rennes.fr
authors.forename: Florian
authors.initials: F
authors.lastname: Lemaitre
authors.forename: Marie
authors.initials: M
authors.lastname: Antignac
authors.forename: Marie-Clémence
authors.initials: MC
authors.lastname: Verdier
authors.forename: Eric
authors.initials: E
authors.lastname: Bellissant
authors.forename: Christine
authors.initials: C
authors.lastname: Fernandez
mesh_terms: D065095:Calcineurin Inhibitors; D016903:Drug Monitoring; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D058570:TOR Serine-Threonine Kinases
keywords: Immunosuppressive drug; Intracellular; Peripheral blood mononuclear cells; Pharmacokinetics; Therapeutic drug monitoring