Florian Lemaitre1,2,3, Nils T Vethe4, Antonio D'Avolio5, Camille Tron1,2,3, Ida Robertsen6, Brenda De Winter7, Amedeo Denicolo5, Birgit C P Koch7, Raman Venkataramanan8, Teun Van Gelder7,9, Mercè Brunet10, Stein Bergan4,6, Dennis A Hesselink9, Pierre Wallemacq11. 1. Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France. 2. Rennes 1 University, Faculty of Medicine, Laboratory of Experimental and Clinical Pharmacology, Rennes, France. 3. Inserm, CIC-P 1414 Clinical Investigation Center, Rennes, France. 4. Department of Pharmacology, Oslo University Hospital, Oslo, Norway. 5. Department of Medical Sciences, University of Turin, Laboratory of Clinical Pharmacology and Pharmacogenetics Padiglione Q, Amedeo, di Savoia Hospital, Turin, Italy. 6. Department of Pharmacy, University of Oslo, Oslo, Norway. 7. Erasmus MC, University Medical Center Rotterdam, Department of Hospital Pharmacy, Rotterdam, The Netherlands. 8. School of Pharmacy, University of Pittsburgh, Pittsburgh, PA. 9. Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam Transplant Group, Rotterdam, The Netherlands. 10. Pharmacology and Toxicology Laboratory, CDB, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Spain; and. 11. Clinical Chemistry Department, Cliniques Universitaires St Luc, Université catholique de Louvain, LTAP, Brussels, Belgium.
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.
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.
Authors: Marith I Francke; Dennis A Hesselink; Yi Li; Birgit C P Koch; Lucia E A de Wit; Ron H N van Schaik; Lin Yang; Carla C Baan; Teun van Gelder; Brenda C M de Winter Journal: Br J Clin Pharmacol Date: 2020-11-24 Impact factor: 4.335