Early acute kidney injury after tacrolimus administration in heart transplant recipients receiving basiliximab induction therapy.

Objective: In this study, we aimed to analyze the association among the timing of tacrolimus initiation, time required to reach the target blood concentration, and early acute kidney injury (AKI) after tacrolimus administration in heart transplant recipients who received basiliximab induction therapy.

Materials And Methods: 88 patients treated with tacrolimus-based immunosuppressive therapy were retrospectively reviewed. Induction therapy was administered to 52 patients.

Risk Assessment of Neutropenia during Low-Dose Valganciclovir Prophylaxis for Heart Transplant Recipients.

The aim of this study was to investigate whether low-dose valganciclovir (VGCV) prophylaxis for cytomegalovirus (CMV) infection increased the risk of developing neutropenia in heart transplant recipients (HTRs). Forty-three HTRs receiving VGCV were divided into two groups: those who received VGCV prophylaxis (n = 22) and those who did not (n = 21). Neutropenia was defined as an absolute neutrophil count ˂1500/µL and was monitored for approximately one year post-transplantation.

Influence of Induction Therapy Using Basiliximab With Delayed Tacrolimus Administration in Heart Transplant Recipients - Comparison With Standard Tacrolimus-Based Triple Immunosuppression.

Background: Appropriate indications and protocols for induction therapy using basiliximab have not been fully established in heart transplant (HTx) recipients. This study elucidated the influence of induction therapy using basiliximab along with delayed tacrolimus (Tac) initiation on the outcomes of high-risk HTx recipients.

Methods and results: A total of 86 HTx recipients treated with Tac-based immunosuppression were retrospectively reviewed.

Relationship between serum bepridil concentration and corrected QT interval.

Objective: Bepridil prolongs the QT interval and can induce torsade de pointes. Although increased bepridil concentration may be a primary cause of prolonged QT, the relationship between serum bepridil concentration and prolonged QT remains unclear. We investigated the relationship between serum bepridil concentration and the corrected QT (QTc) interval in patients treated with bepridil.

Drug interactions between tacrolimus and clotrimazole troche: a data mining approach followed by a pharmacokinetic study.

Purpose: This study investigated the effects of clotrimazole troche on the risk of transplant rejection and the pharmacokinetics of tacrolimus.

Methods: The data mining approach was used to investigate whether the use of clotrimazole increased the risk of transplant rejection in patients receiving tacrolimus therapy. Patient data were acquired from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2017.

Comparison of CYP3A5*3 genotyping assays for personalizing immunosuppressive therapy in heart transplant patients .

Objective: This study aimed to compare a novel point-of-care assay that involves a flap endonuclease reaction performed using GTS-7000 to a conventional assay that involves DNA sequencing performed using 3130xl Genetic Analyzers*.

Materials And Methods: This study enrolled 74 patients who underwent heart transplantation at the National Cerebral and Cardiovascular Center between May 2004 and October 2016. Each patient was genotyped as cytochrome P450 (CYP) 3A5*1/*1, -CYP3A5*1/*3, or CYP3A5*3/*3.

De novo malignancy in heart transplant recipients: A single center experience in Japan.

Background: Because of aggressive immunosuppression, heart transplant recipients have a high risk of de novo malignancy, which is a major cause of death and worse prognosis, regardless of the type. However, the impact of de novo malignancy on Japanese heart transplant recipients is unknown.

Methods: We analyzed 103 Japanese heart transplant recipients over 18-years-old at the time of transplantation between April 1999 and April 2017.

Impact of Coronary Artery Calcification in the Donor Heart on Transmitted Coronary Artery Disease in Heart Transplant Recipients.

Background: Coronary artery disease (CAD) after heart transplantation (HTx) develops as a combination of donor-transmitted coronary atherosclerosis (DTCA) and cardiac allograft vasculopathy. Assessing donor CAD before procurement is important. Because coronary artery calcification (CAC) is a predictor for CAD, donor-heart CAC is usually evaluated to estimate the risk of donor CAD.

Effects of clotrimazole on tacrolimus pharmacokinetics in patients with heart transplants with different CYP3A5 genotypes.

Purpose: This study aimed to investigate the effects of clotrimazole on the pharmacokinetics of tacrolimus in Japanese patients with heart transplants with different CYP3A5 genotypes.

Methods: Twenty-six patients who underwent heart transplantation between June 2012 and July 2017 were enrolled in this retrospective study. The CYP3A5 (rs776746; CYP3A5*3) genotype was determined after monitoring and analysing tacrolimus blood concentrations.

Changes in blood concentration of mycophenolic acid and FK506 in a heart-transplant patient treated with plasmapheresis .

Objective: Prior to heart transplant, sensitization to human leukocyte antigen can occur after blood transfusions used during implantation of ventricular assist devices. The result is an increased risk of antibody-mediated rejection (AMR) after heart transplant. While plasmapheresis (PPH) treats serious AMR cases, what subsequent changes occur in the blood concentrations of immunosuppressive agents is still unknown.

Effects of vitamin K epoxide reductase complex 1 gene polymorphisms on warfarin control in Japanese patients with left ventricular assist devices (LVAD).

Purpose: This study aimed to investigate relationships between times in therapeutic range (TTR) or warfarin sensitivity indexes (WSI) and VKORC1-1639G>A and CYP2C9 polymorphisms in patients with left ventricular assist devices (LVAD).

Methods: Severe heart failure patients who received LVAD from January 1, 2013 to October 31, 2017 were recruited. Relationships between TTR or WSI and VKORC1-1639G>A and CYP2C9 gene polymorphisms were investigated immediately after LVAD implantation (period 1) and immediately prior to hospital discharge (period 2).

Impact of the CYP3A5*1 Allele on the Pharmacokinetics of Tacrolimus in Japanese Heart Transplant Patients.

Background And Objective: Tacrolimus, a major immunosuppressant used after transplantation, is associated with large interindividual variation involving genetic polymorphisms in metabolic processes. A common variant of the cytochrome P450 (CYP) 3A5 gene, CYP3A5*3, affects blood concentrations of tacrolimus. However, tacrolimus pharmacokinetics at the early stage of transplantation have not been adequately studied in heart transplantation.

Effect of fluconazole on the pharmacokinetics of everolimus and tacrolimus in a heart transplant recipient: Case report.

Objective: Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) and has been used in combination with calcineurin inhibitors (tacrolimus and cyclosporine) to prevent allograft rejection following organ transplantation. In heart transplant recipients, everolimus should be maintained at a target blood concentration of 3 - 8 ng/mL, in combination with reduced-dose calcineurin inhibitors and therefore, requires strict monitoring. Fluconazole, an azole antifungal agent, affects blood concentration of tacrolimus by inhibiting the cytochromes P450 (CYP) 3A4 and 3A5.

Use of rifabutin to treat tuberculosis in a cardiac transplant recipient: A case report .

Objective: Tuberculosis is an important concern following organ transplantation. Unfortunately, several antituberculosis drugs interact with immunosuppressants. This report describes our experience with rifabutin (RBT) in the treatment of acute tuberculosis in a cardiac transplant recipient.

Gastrointestinal risk factors and prescribing pattern of antiulcer agents in patients taking low-dose aspirin in Japan.

Objectives: To identify prescribing patterns of antiulcer agents in patients on low-dose aspirin (LDA) and to evaluate the number of gastrointestinal (GI) risk factors of the patients.

Methods: A retrospective chart review of patients taking LDA was conducted at the National Cerebral and Cardiovascular Center in Japan. The rate of concomitant use of antiulcer agents and the risk of each patient to develop GI complications were evaluated.

Association between Serum Amiodarone and N-Desethylamiodarone Concentrations and Development of Thyroid Dysfunction.

Objective: This retrospective cohort study was performed to examine the association between serum amiodarone (AMD) and N-desethylamiodarone (DEA) concentrations and the development of thyroid dysfunction.

Methods: Patients treated with AMD from January 2012 to April 2016 were identified from the computerized hospital information system database at the National Cerebral and Cardiovascular Center. Only patients whose serum AMD and DEA concentrations had been determined at least once were included in the study.

The influence of residual apixaban on bleeding complications during and after catheter ablation of atrial fibrillation.

Background: The periprocedural protocol for atrial fibrillation (AF) ablation commonly includes anticoagulation therapy. Apixaban, a direct oral anticoagulant, is currently approved for clinical use; however, little is known about the effects of residual apixaban concentration on bleeding complications during/after AF ablation. Therefore, we measured residual apixaban concentration by using mass spectrometry and examined the anticoagulant's residual effects on bleeding complications.

Tacrolimus Triggers Transient Receptor Potential Vanilloid-1-Dependent Relapse of Pancreatitis-Related Pain in Mice.

Transient receptor potential vanilloid-1 (TRPV1) expressed in nociceptors is directly phosphorylated and activated by protein kinase C, and involved in the signaling of pancreatic pain. On the other hand, Cav3.2 T-type Ca2+ channels expressed in nociceptors are functionally upregulated by phosphorylation with protein kinase A and also play a role in pancreatitis-related pain.

Association between N-desethylamiodarone/amiodarone ratio and amiodarone-induced thyroid dysfunction.

Purpose: We used a retrospective data mining approach to explore the association between serum amiodarone (AMD) and N-desethylamiodarone (DEA) concentrations and thyroid-related hormone levels.

Methods: Laboratory data sets from January 2012 to April 2016 were extracted from the computerized hospital information system database at the National Cerebral and Cardiovascular Center (NCVC). Data sets that contained serum AMD and DEA concentrations and thyroid function tests, including thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3), were analyzed.

Risk factors for amiodarone-induced thyroid dysfunction in Japan.

Background: Amiodarone is associated with a number of significant adverse effects, including elevated transaminase levels, pulmonary fibrosis, arrhythmia, and thyroid dysfunction. Although thyroid dysfunction is considered to be a common and potentially serious adverse effect of amiodarone therapy, the exact pathogenesis remains unknown because of its complex manifestations. Therefore, the prevalence of, and risk factors for, amiodarone-induced thyroid dysfunction in Japanese patients were investigated in the present study.

Circadian pharmacokinetics and limited sampling strategy of everolimus in heart transplant patients .

Objective: To evaluate circadian changes in everolimus (EVL) pharmacokinetics and to identify the time point of blood sampling with the strongest correlation with the area under the blood concentration-time curve (AUC) of EVL in heart transplant patients.

Methods: Heart transplant patients receiving the same dose of EVL twice a day were reviewed. In 28 patients enrolled, whole blood samples were collected before (C0), and 1, 2, 4, 6, 8, and 12 hours after each administration of EVL.