title: Intra-patient variability in tacrolimus exposure: causes, consequences for clinical management.
abstract: Tacrolimus (Tac) is widely used for the prevention of rejection after solid organ transplantation. Finding the optimal balance between effective Tac concentrations and toxicity is a challenge and requires therapeutic drug monitoring. In addition to the well-known inter-patient variability, the clinical use of Tac is also complicated by considerable intra-patient variability (IPV) in Tac exposure. Tac IPV is defined as the amount of fluctuation of whole-blood concentrations over a certain period of time during which the Tac dose remains unchanged. A high IPV in Tac exposure has recently been recognized as a strong risk factor for acute rejection and poor long-term kidney transplantation outcome. In addition to non-adherence, several other factors determine the magnitude of the IPV in Tac exposure. Quantification of IPV is easy and can be easily incorporated into everyday clinical practice as a tool for optimizing transplantation outcomes.
authors: Department of Internal Medicine, Division of Nephrology and Renal Transplantation, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Hospital Pharmacy, Clinical Pharmacology Unit, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. Electronic address: n.shuker@erasmusmc.nl.
authors: Nauras
authors: N
authors: Shuker
authors: Department of Internal Medicine, Division of Nephrology and Renal Transplantation, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Hospital Pharmacy, Clinical Pharmacology Unit, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors: Teun
authors: T
authors: van Gelder
authors: Department of Internal Medicine, Division of Nephrology and Renal Transplantation, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors: Dennis A
authors: DA
authors: Hesselink
mesh_terms: D016903:Drug Monitoring; D006084:Graft Rejection / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus