Search results for "Tacrolimus"
showing 10 items of 89 documents
Hepatitis C virus viral kinetics during α-2a or α-2b pegylated interferon plus ribavirin therapy in liver transplant recipients with different immuno…
2012
Abstract Background Predictors of sustained virological response (SVR) to antiviral therapy post-liver transplantation (LT) for chronic hepatitis C are needed. In non-transplanted patients, viral kinetics can predict SVR. Objectives To determine the early viral kinetics in LT recipients with different immunosuppression (tacrolimus – Tac- vs. cyclosporine – CsA-) during treatment with peg-IFN + RBV. Study design Prospective pilot study in HCV-1b infected patients: (LT CsA n = 8; Tac n = 8; non-LT n = 4), treated with IFN α-2a vs. α-2b (180 μg or 1.5 μg/kg, respectively) once weekly plus weight-based RBV. Median CsA or Tac baseline trough levels were 141 and 7.70 ng/mL, respectively. HCV-RNA …
Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation.
2015
Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients). The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc). The ABCB1 variant in rs1045642 was associated with significantly hig…
Meta-analysis and systematic review of the effect of the donor and recipient CYP3A5 6986A>G genotype on tacrolimus dose requirements in liver tran…
2013
Objective A meta-analysis was carried out of publishedstudies on the effect of the CYP3A5 6986A>Gpolymorphism in liver donors and transplant recipientson tacrolimus pharmacokinetics.Methods Cohort studies that evaluated the relationshipbetween the CYP3A5 polymorphism in liver donors andtransplant recipients and tacrolimus, trough bloodconcentration normalized for the daily dose (C) perkilogram body weight (D) (C/D, ng/ml/mg/kg/day) up to1 year after transplantation, were included. Data were notrestricted by patient age or the language or journal ofpublication. A literature search was conducted using theCochrane Library, MEDLINE, EMBASE, and grey literature,and articles published up to 24 Ap…
Feasibility of thiotepa addition to the fludarabine-busulfan conditioning with tacrolimus/sirolimus as graft vs host disease prophylaxis.
2020
In classical reduced-intensity conditioning (RIC) regimens, including the fludarabine and busulphan (BF) combination, sirolimus and tacrolimus (SIR-TAC) as graft vs host disease (GVHD) prophylaxis has shown acceptable results. The outcomes of SIR-TAC in a more intense RIC regimen as Thiotepa-fludarabine-busulfan (TBF) have been hardly investigated. This retrospective study included all consecutive patients receiving an allogeneic hematopoietic stem cell transplantation for myeloid malignancies (January 2009-2017) conditioned with either TBF or BF and receiving SIR-TAC. Patients receiving TBF presented higher non-relapse mortality (31.6 vs 12.3%,p = .01), along with shorter overall survival …
Contribution of CYP3A5 to the in vitro hepatic clearance of tacrolimus.
2005
Abstract Background: Tacrolimus is metabolized predominantly to 13-O-demethyltacrolimus in the liver and intestine by cytochrome P450 3A (CYP3A). Patients with high concentrations of CYP3A5, a CYP3A isoenzyme polymorphically produced in these organs, require higher doses of tacrolimus, but the exact mechanism of this association is unknown. Methods: cDNA-expressed CYP3A enzymes and a bank of human liver microsomes with known CYP3A4 and CYP3A5 content were used to investigate the contribution of CYP3A5 to the metabolism of tacrolimus to 13-O-demethyltacrolimus as quantified by liquid chromatography–tandem mass spectrometry. Results: Demethylation of tacrolimus to 13-O-demethyltacrolimus was …
Stability of tacrolimus ophthalmic solution
2017
Purpose The stability of 0.3-mg/mL tacrolimus ophthalmic solution at different storage temperatures was studied. Methods A sterile ophthalmic solution of 0.3 mg/mL tacrolimus was prepared in triplicate under aseptic conditions by diluting tacrolimus in eye drops. Three aliquots of this solution were transferred into polypropylene bottles and stored at 25, 2–8, or −15 to −25 °C. Samples were collected immediately after preparation and at selected time points and assayed in triplicate using high-performance liquid chromatography (HPLC). Samples were also visually examined for macroscopic changes. The 0.3-mg/mL tacrolimus solution was also exposed to acidic treatment and heat to force its degr…
A mild form of rituximab-associated lung injury in two adolescents treated for nephrotic syndrome: Table 1
2015
Rituximab is used as a steroid/calcineurin inhibitor-saving agent in patients with nephrotic syndrome. Safety is a crucial issue for justifying widespread use of the drug in this clinical setting. Rituximab-associated lung injury (RALI) is a severe and potentially life-threatening complication in oncohaematological and rheumatological patients, while it has only been anecdotally reported in association with idiopathic nephrotic syndrome (2 cases described, 1 with fatal outcome). We describe a benign form of RALI occurring in two adolescents treated with rituximab (single pulse of 375 mg/m2) for nephrotic syndrome. Before treatment, the patients were in good clinical condition while receivin…
Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial
2012
In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced-exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (-3.0%; 95% CI -8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in…
Suppression of allograft rejection in the sponge Suberites domuncula by FK506 and expression of genes encoding FK506-binding proteins in allografts.
2001
SUMMARY Porifera (sponges) are, evolutionarily, the oldest metazoan phylum. Recent molecular data suggest that these animals possess molecules similar to and homologous with those of the innate and adaptive immune systems of higher Metazoa. Applying the biological system of parabiosis and the technique of differential display of mRNA, two cDNAs encoding putative FK506-binding proteins were isolated. FK506 is successfully used in clinics as a drug to prevent allograft rejection and is toxic to Suberites domuncula cells in vitro at doses above 100ng ml−1. Autograft fusion of transplants from S. domuncula was not affected by FK506. Allograft non-fusion was not affected by FK506 at toxic doses;…
Patient outcomes in two steroid-free regimens using tacrolimus monotherapy after daclizumab induction and tacrolimus with mycophenolate mofetil in li…
2008
Introduction. Long-term steroid administration may predispose liver transplant recipients to infectious and metabolic complication. Maintaining effective immunoprophylaxis while minimizing the negative consequences of steroid therapy could be a key factor in improving clinical outcomes.Methods. Six hundred two patients were randomized to receive tacrolimus (TAC) immunosuppression with a single-steroid bolus and two doses of daclizumab (DAC) or mycophenolate mofetil (MMF).Results. The incidence of biopsy-proven acute rejection was 19.7% in the TAC/DAC group and 16.2% in the TAC/ MMF group (ns). Three-month patient and graft survival were similar. Steroid use at month-3 was low at 5.5% in the…