Track topics on Twitter Track topics that are important to you
Most lung transplantation immunosuppression regimens include tacrolimus. Single nucleotide polymorphisms (SNPs) in genes important to tacrolimus bioavailability and clearance (ABCB1, CYP3A4 and CYP3A5) are associated with differences in tacrolimus pharmacokinetics. We hypothesized that polymorphisms in these genes would impact immunosuppression-related outcomes. We categorized ABCB1, CYP3A4, and CYP3A5 SNPs for 321 lung allograft recipients. Genotype effects on time to therapeutic tacrolimus level, interactions with antifungal medications, concentration to dose (C /D), acute kidney injury, and rejection were assessed using linear models adjusted for subject characteristics and repeat measures. Compared with CYP3A poor metabolizers (PM), time to therapeutic tacrolimus trough was increased by 5.1±1.6 days for CYP3A extensive metabolizers (EM, p<0.001). In the post-operative period, CYP3A intermediate metabolizers spent 1.2±0.5 days less (p=0.01) and EM spent 2.1±0.5 days less (p<0.001) in goal tacrolimus range than CYP3A PM. Azole antifungals interacted with CYP3A genotype in predicting C /D (p<0.001). Increased acute kidney injury rates were observed in subjects with high ABCB1 function (OR 3.0, 95% CI 1.1-8.6, p=0.01). Lower rates of acute cellular rejection were observed in subjects with low ABCB1 function (OR 0.36, 95% CI 0.07-0.94, p=0.02). Recipient genotyping may help inform tacrolimus dosing decisions and risk of adverse clinical outcomes. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: Clinical transplantation
Membrane transporters play an essential role in the pharmacokinetics of drugs as they mediate exchanges between biological compartments. Tacrolimus is characterized by wide interpatient variability in...
Conversion from Twice-Daily Prograf to Once-Daily Advagraf in Multi-ethnic Asian Adult Renal Transplant Recipients With or Without Concomitant Use of Diltiazem: Impact of CYP3A5 and MDR1 Genetic Polymorphisms on Tacrolimus Exposure.
Tacrolimus is the mainstay of immunosuppression in renal transplantation. Given that once-daily administration improves patient compliance, 1:1 dose conversion from twice-daily Prograf to once-daily A...
The aims of this study were to describe the pharmacokinetics of tacrolimus immediately after kidney transplantation, and to develop a clinical tool for selecting the best starting dose for each patien...
Tacrolimus, a calcineurin inhibitor, is a common immunosuppressant prescribed after organ transplantation and has notable inter- and intrapatient pharmacokinetic variability. The sources of variabilit...
Tacrolimus has been associated with notable extrarenal adverse effects (AEs), which are unpredictable and impact patient morbidity. The association between model-predicted tacrolimus exposure metrics ...
The purpose of the study is to identify factors that may influence tacrolimus (TAC) pharmacokinetics, and the impact of gene polymorphism (ABCB1, CYP3A4, CYP3A5, POR) on pharmacokinetics o...
The purpose of this study is to evaluate the effect that telaprevir has on the pharmacokinetics of cyclosporine and tacrolimus. Pharmacokinetics means how the drug is absorbed into the bl...
the present study was conducted to assess the population pharmacokinetics of tacrolimus in children with nephrotic syndrome and to use these data to calculate an optimal dosing regimen of ...
The purpose of this study is to understand whether the pharmacokinetics of tacrolimus is influenced by the concurrent use of sirolimus.
Pharmacokinetics of tacrolimus are highly variable and may result in graft rejection (underdosing) or toxicity (overdosing). The risk of transplant rejection and the toxicity of tacrolimu...
A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.
A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS. EC 5.2.1.-
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that TACROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
The attempt to improve the PHENOTYPES of future generations of the human population by fostering the reproduction of those with favorable phenotypes and GENOTYPES and hampering or preventing BREEDING by those with "undesirable" phenotypes and genotypes. The concept is largely discredited. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza, Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...
Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...