Original ArticleMeasuring Intracellular Concentrations of Calcineurin Inhibitors: Expert Consensus from the International Association of Therapeutic Drug Monitoring and Clinical Toxicology Expert PanelLemaitre, Florian PhD*,†,‡; Vethe, Nils T. PhD§; D'Avolio, Antonio PhD¶; Tron, Camille PhD*,†,‡; Robertsen, Ida PhD║; De Winter, Brenda PhD*,*; Denicolo, Amedeo PhD¶; Koch, Birgit C. P. PhD*,*; Venkataramanan, Raman PhD†,†; Van Gelder, Teun PhD*,*,‡,‡; Brunet, Mercè PhD§,§; Bergan, Stein PhD§,║; Hesselink, Dennis A. PhD‡,‡; Wallemacq, Pierre PhD¶,¶ Author Information *Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France; †Rennes 1 University, Faculty of Medicine, Laboratory of Experimental and Clinical Pharmacology, Rennes, France; ‡Inserm, CIC-P 1414 Clinical Investigation Center, Rennes, France; §Department of Pharmacology, Oslo University Hospital, Oslo, Norway; ¶Department of Medical Sciences, University of Turin, Laboratory of Clinical Pharmacology and Pharmacogenetics Padiglione Q, Amedeo, di Savoia Hospital, Turin, Italy; ║Department of Pharmacy, University of Oslo, Oslo, Norway; **Erasmus MC, University Medical Center Rotterdam, Department of Hospital Pharmacy, Rotterdam, The Netherlands; ††School of Pharmacy, University of Pittsburgh, Pittsburgh, PA; ‡‡Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam Transplant Group, Rotterdam, The Netherlands; §§Pharmacology and Toxicology Laboratory, CDB, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Spain; and ¶¶Clinical Chemistry Department, Cliniques Universitaires St Luc, Université catholique de Louvain, LTAP, Brussels, Belgium. Correspondence: Florian Lemaitre, PhD, Laboratoire de Pharmacologie, Hôpital Pontchaillou, CHU de Rennes, 2, rue Henri Le Guilloux, 35033 Rennes cedex, France (e-mail: [email protected]). F. Lemaitre has received research grants from Astellas Pharma, Chiesi Pharma, and Sandoz and support for attending meetings from Sandoz; T. Van Gelder has received study grant from Chiesi and is on speaker bureau of Astellas; M. Brunet has received a research grant from Chiesi Pharma, honoraria for presentation from Astellas Pharma, and support for attending meetings from Novartis and Astellas Pharma; D. A. Hesselink has received lecture and consulting fees from Astellas Pharma, Chiesi Pharma, and Novartis Pharma, as well as grant support from Astellas Pharma and Chiesi Pharma (paid to his institution). Remaining authors declare no conflict of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.drug-monitoring.com). Therapeutic Drug Monitoring: October 2020 - Volume 42 - Issue 5 - p 665-670 doi: 10.1097/FTD.0000000000000780 Buy SDC Metrics Abstract Background: Therapeutic drug monitoring (TDM) of the 2 calcineurin inhibitors (CNIs), tacrolimus (TAC) and cyclosporin A, has resulted in improvements in the management of patients who have undergone solid organ transplantation. As a result of TDM, acute rejection (AR) rates and treatment-related toxicities have been reduced. Irrespective, AR and toxicity still occur in patients who have undergone transplantation, showing blood CNI concentrations within the therapeutic range. Moreover, the AR rate is no longer decreasing. Hence, smarter TDM approaches are necessary. Because CNIs exert their action inside T lymphocytes, intracellular CNIs may be a promising candidate for improving therapeutic outcomes. The intracellular CNI concentration may be more directly related to the drug effect and has been favorably compared with the standard, whole-blood TDM for TAC in liver transplant recipients. However, measuring intracellular CNIs concentrations is not without pitfalls at both the preanalytical and analytical stages, and standardization seems essential in this area. To date, there are no guidelines for the TDM of intracellular CNI concentrations. Methods: Under the auspices of the International Association of TDM and Clinical Toxicology and its Immunosuppressive Drug committees, a group of leading investigators in this field have shared experiences and have presented preanalytical and analytical recommendations for measuring intracellular CNI concentrations. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.