A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants.

Aims: We aimed to evaluate bleeding risk in clinical practice in patients with atrial fibrillation (AF) being prescribed dabigatran, rivaroxaban, or apixaban compared with warfarin.

Methods: Using nationwide registries (Norwegian Patient Registry and Norwegian Prescription Database), we identified AF patients with a first prescription of oral anticoagulants between January 2013 and June 2015. Patients were followed until discontinuation or switching of oral anticoagulants, death, or end of follow-up.

Closer to the Site of Action: Everolimus Concentrations in Peripheral Blood Mononuclear Cells Correlate Well With Whole Blood Concentrations.

Background: Everolimus (EVE) is an immunosuppressive drug dosed according to therapeutic drug monitoring in renal transplant recipients. The primary site of action is within activated lymphocytes. EVE is a substrate of the efflux transporter ABCB1 also known as P-glycoprotein.

Endomyocardial, intralymphocyte, and whole blood concentrations of ciclosporin A in heart transplant recipients.

Background: In the early phases following heart transplantation a main challenge is to reduce the impact of acute rejections. Previous studies indicate that intracellular ciclosporin A (CsA) concentration may be a sensitive acute rejection marker in renal transplant recipients. The aims of this study were to evaluate the relationships between CsA concentrations at different target sites as potential therapeutic drug monitoring (TDM) tools in heart transplant recipients.

Urinary proteomic shotgun approach for identification of potential acute rejection biomarkers in renal transplant recipients.

Background: Acute rejection (AR) episodes in renal transplant recipients are suspected when plasma creatinine is elevated and other potential causes out ruled. Graft biopsies are however needed for definite diagnosis. Non-invasive AR-biomarkers is an unmet clinical need.

The concentration of cyclosporine metabolites is significantly lower in kidney transplant recipients with diabetes mellitus.

Background: Diabetes mellitus is prevalent among kidney transplant recipients. The activity of drug metabolizing enzymes or transporters may be altered by diabetes leading to changes in the concentration of parent drug or metabolites. This study was aimed to characterize the effect of diabetes on the concentration of cyclosporine (CsA) and metabolites.

Computer-assisted cyclosporine dosing performs better than traditional dosing in renal transplant recipients: results of a pilot study.

Cyclosporine A (CsA) is widely used after organ transplantation. Its narrow therapeutic window and large pharmacokinetic variability makes therapeutic drug monitoring (TDM) demanding and frequent dose adjustments are needed, especially early after transplantation. The aim of the present pilot study was to compare accuracy of CsA TDM by experienced clinicians against a computer-assisted dosing model.

A population pharmacokinetic model of ciclosporin applicable for assisting dose management of kidney transplant recipients.

Background And Objective: The pharmacokinetic disposition of ciclosporin shows great intra- and interpatient variability, and that combined with a narrow therapeutic window makes therapeutic drug monitoring of ciclosporin necessary. The nonlinear mixed-effects population pharmacokinetic program NONMEM predicts individual pharmacokinetic parameters based not only on individual patient observations but also on population characteristics and the patient's covariates. The aim of this model development is to potentially use it in the clinical setting to optimize ciclosporin dosing in renal transplant recipients.

Reduced elimination of cyclosporine A in elderly (>65 years) kidney transplant recipients.

Background: Physiologic functions that may affect pharmacokinetics of drugs are altered in elderly patients. The current study was performed to elucidate the effect of age on cyclosporine A (CsA) pharmacokinetics in renal transplant recipients.

Method: Twenty-five renal transplant recipients on CsA treatment were included in the study.

Declining intracellular T-lymphocyte concentration of cyclosporine a precedes acute rejection in kidney transplant recipients.

Background: We investigated cyclosporine A (CsA) concentrations at the site of action, inside T-lymphocytes, to evaluate its applicability as a new supplementary therapeutic drug monitoring method after renal transplantation.

Method: In this prospective single-center study, 20 kidney transplant recipients, mean age 54 (range 21-74) years, on CsA-based immunosuppression were included within 2 weeks posttransplant and followed for 3 months. Nine patients also had one full 12-hour pharmacokinetic profile performed.

Cinacalcet's effect on the pharmacokinetics of tacrolimus, cyclosporine and mycophenolate in renal transplant recipients.

Background: The calcimimetic drug cinacalcet offers a novel therapeutic option to treat post-transplant hypercalcemia and hyperparathyroidism; however, the interaction with calcineurin inhibitors and mycophenolate has not been evaluated.

Methods: In the present study the effects of cinacalcet on the pharmacokinetics of cyclosporine A (CsA), tacrolimus (Tac) and mycophenolate were investigated in 14 renal transplant recipients with stable renal function (mean creatinine 126.4 +/- 45.

Determination of ciclosporin A and its six main metabolites in isolated T-lymphocytes and whole blood using liquid chromatography-tandem mass spectrometry.

A specific and sensitive method for determination of intracellular ciclosporin A (CsA) and its six main metabolites AM1, AM9, AM1c, AM1c9, AM19 and AM4N, in isolated T-lymphocytes and whole blood is described. T-lymphocytes were separated from whole blood using Prepacyte. The analytes were extracted and purified from isolated lymphocytes and whole blood by protein precipitation followed by solid-phase extraction (SPE).