Meltdose Tacrolimus Pharmacokinetics M. Baraldo* Department of Experimental and Clinical Medicine, Medical School, University of Udine; SOC Institute of Clinical Pharmacology, University-Hospital S. Maria della Misercordia, Udine, Italy ABSTRACT Background. Nonadherence to immunosuppressive therapy contributes to the loss of grafts. One of the problem is the fractioning of immunosuppressive dose. In fact, it was demonstrated that a single daily dose (QD) is associated with an increased adherence to therapy compared with twice daily dosing (BID). Tacrolimus (TAC), calcineurin inhibitor, is one of immunosuppression pillar in organ transplantation and its action is strongly correlated with blood concentration and therefore the therapeutic drug monitoring is recommended in the guidelines. However, one of the critical points of TAC is the poor and variable bioavailability that influences immunosuppression, and is also responsible for adverse effects. Methods. MeltDoseÒ Technology is a new technology to improve efficacy and/or reduce side effects. This new technology applied to TAC (EnvarsusÒ or LCP-TAC) has achieved 4 main objectives: (1) improved bioavailability, (2) reduced dose fractioning to one tablet per day, (3) limited variability concentrations of TAC, and (4) lower doses of TAC will be administered. Results. We analyzed the pharmacokinetic profile, efficacy, and security of EnvarsusÒ. T ACROLIMUS (TAC), calcineurin inhibitor, is a pillar of immunosuppression in organ transplantation and it has as an immediate release (IR) formulation requiring a twice daily dose regimen (BID). Its action is associated strongly with blood concentration and therefore the actual guidelines recommended therapeutic drug monitoring [1]. One of the critical points of TAC-IR, is the poor and variable bioavailability [2,3]. Because the maximum drug concentration (C max ) and area under the curve (AUC 0e12 ) are fundamental to immunosuppression, but are also responsible for adverse effects (nephrotoxicity, tremor and paresthesia, hypertension, hyperglycemia), these parameters strongly affect the graft and patient health [4]. A review showing the results of 10 cohort studies con- ducted on kidney transplants (KTx) indicates that, in transplant recipients, nonadherence to immunosuppressive therapy contributes to the loss of grafts. Published data indicate that it can be up to 36% loss of the graft, a 7-fold increase compared with compliant patients [5,6]. In KTx, poor adherence to therapy seems to be linked closely with the dose fractioning of the drug; that is, the higher the dose fractionation, the lower is the adherence. Therefore, a single daily dose (QD) is associated with an increased adherence to therapy compared with a BID schedule [7]. So the second type of TAC was a prolonged- released capsules (TAC-PR) administered as single daily dose. This new formulation, however, did not solve the problem of interindividual and intraindividual variability, which is linked with lesser bioavailability. Nanotechnology and nanoformulations in medicine can overcome the problems of poor bioavailability by virtue of the nanosize of drugs [8]. An extended-release formula- tion of TAC designed for once-daily administration (LCP- TAC) is a new prolonged-release TAC formulation, using a drug delivery technology designed to enhance the bioavailability of drugs with low water solubility by creating a solid solution of the drug. This minireview analyzes the pharmacokinetic properties of LCP-TAC in transplant recipients, omitting aspects of efficacy and safety of the new formulation. *Address correspondence to Baraldo Massimo MD, Associate Professor of Pharmacology, SOC Institute of Clinical Pharma- cology, University-Hospital S. Maria della Misercordia, 25, 33100 Udine, Italy. E-mail: massimo.baraldo@uniud.it 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.02.002 ª 2016 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 420 Transplantation Proceedings, 48, 420e423 (2016)