Tacrolimus

Plosker, Greg L.; Foster, Rachel H.

doi:10.2165/00003495-200059020-00021

Cited by 269 publications

(42 citation statements)

References 292 publications

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“…2, Table 2). It has been known that tacrolimus specifically inhibit T cell activation via impairment of calcineurin activity, 10) and therefore, the drug might exhibit relatively a low efficacy to suppress proliferation of PBMCs with low T cell activity. Thus, the efficacy of tacrolimus to inhibit proliferation might be high in PBMCs with high T cell activities (high stimulation indices) and vice versa.…”

Section: Discussionmentioning

confidence: 99%

Pharmacodynamic Parameters of Immunosuppressive Drugs Are Not Correlated with Age, Duration of Dialysis, Percentage of Lymphocytes or Lymphocyte Stimulation Index in Renal Transplant Recipients

Sugiyama

Isogai

Toyama

et al. 2008

Biological & Pharmaceutical Bulletin

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Immunosuppressive agents, including calcineurin inhibitors, exhibit individual variation in their therapeutic efficacies in allograft recipients. In general, therapeutic drug monitoring (TDM) of cyclosporine or tacrolimus is performed to examine the dosing of drugs that should be used to optimize immunosuppressive therapy. However, it is not always possible to prevent allograft rejection after transplantation regardless of TDM-based immunosuppressive therapy. This fact suggested that the large individual variation in clinical efficacy of immunosuppressants is attributed to individual differences in not only pharmacokinetic but also pharmacodynamic parameters of the drugs.This study employed a lymphocyte immunosuppressant sensitivity test (LIST) to evaluate the pharmacodynamic properties of immunosuppressive agents. [1][2][3][4][5][6][7] LIST is an assay to evaluate the pharmacological efficacy of immunosuppressive drugs in-vitro using the peripheral-blood mononuclear cells (PBMCs) of transplant recipients. In this assay, PBMCs were incubated in the presence of concanavalin A and the immunosuppressive agents, and the concentration-dependent inhibitory effects of the drugs on concanavalin A-stimulated PBMC blastogenesis were measured. It was reported previously that the IC 50 values of prednisolone against blastogenesis varied widely among patients, and the IC 50 values correlated with the clinical efficacy of this drug in renal transplantation.1) On the other hand, the pharmacological efficacy of immunosuppressive agents may also be affected by the immunological state of patients. Agerelated deterioration in immune function, termed immunosenescence, has been recognized for decades. Hemodialysis or peritoneal dialysis has been suggested to contribute to oxidative stress in patients, and dialysis may modulate immune functions through an increase in reactive oxygen species. The percentage of lymphocytes to total white blood cells and blastogenesis stimulation index (i.e., the ratio of lymphocyte proliferation stimulated and unstimulated by concanavalin A) are also related to immunoactivity. If the efficacy (pharmacodynamics) of immunosuppressive agents correlates with age, duration of dialysis, percentage of lymphocytes, or stimulation index, the correlations will contribute to the development of tailored immunosuppressive therapies.In order to examine the relationship between the efficacy of immunosuppressive drugs and patient characteristics or laboratory diagnostic data, in the present study the IC 50 values of 6 drugs, cyclosporine, tacrolimus, methylprednisolone, 6-mercaptopurine, mycophenolic acid, and mizoribine were measured in 29 renal transplant recipients using LIST. Then, the data of IC 50 values were examined for their relation with each 4 factors; age, duration of dialysis, percentage of lymphocytes in total white blood cells, and blastogenesis stimulation index by mitogen. MATERIALS AND METHODSMaterials Cyclosporine, tacrolimus, and mizoribine were kindly provided by Novartis (Basel, Switzerland), Ast...

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Section: Discussionmentioning

confidence: 99%

Pharmacodynamic Parameters of Immunosuppressive Drugs Are Not Correlated with Age, Duration of Dialysis, Percentage of Lymphocytes or Lymphocyte Stimulation Index in Renal Transplant Recipients

Sugiyama

Isogai

Toyama

et al. 2008

Biological & Pharmaceutical Bulletin

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“…FK506 (also known as Tacrolimus) is an immunosuppressive drug with a known pharmacokinetic and toxicity profile. It is widely used in solid organ transplantations to lower the risk of organ rejection [164]. High doses of FK506 caused systemic hypertension and transplant vasculopathy in animal models [165].…”

Section: Restoring Bmprii Signaling As a Therapeutic Strategymentioning

confidence: 99%

BMP type II receptor as a therapeutic target in pulmonary arterial hypertension

Orriols

Gomez‐Puerto

Dijke

2017

Cell. Mol. Life Sci.

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Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary arterial pressure. This occurs due to abnormal remodeling of small peripheral lung vasculature resulting in progressive occlusion of the artery lumen that eventually causes right heart failure and death. The most common cause of PAH is inactivating mutations in the gene encoding a bone morphogenetic protein type II receptor (BMPRII). Current therapeutic options for PAH are limited and focused mainly on reversal of pulmonary vasoconstriction and proliferation of vascular cells. Although these treatments can relieve disease symptoms, PAH remains a progressive lethal disease. Emerging data suggest that restoration of BMPRII signaling in PAH is a promising alternative that could prevent and reverse pulmonary vascular remodeling. Here we will focus on recent advances in rescuing BMPRII expression, function or signaling to prevent and reverse pulmonary vascular remodeling in PAH and its feasibility for clinical translation. Furthermore, we summarize the role of described miRNAs that directly target the BMPR2 gene in blood vessels. We discuss the therapeutic potential and the limitations of promising new approaches to restore BMPRII signaling in PAH patients. Different mutations in BMPR2 and environmental/genetic factors make PAH a heterogeneous disease and it is thus likely that the best approach will be patient-tailored therapies.

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“…On the other hand, persons with alleles connected with increased rate of drug metabolism may require higher drug doses to fully benefit from its effects. There are several types of drugs used in the treatment of renal disorders that are characterized by a high variability in pharmacokinetic behaviour and by a poor correlation between drug concentrations and pharmocodynamic effects [80,81,82,83]. Therefore there is a need to “tailor” the dose of these drugs to avoid toxicity and to obtain full efficacy.…”

Section: Treatment Of Renal Diseasesmentioning

confidence: 99%

Personalized Medicine: New Perspectives for the Diagnosis and the Treatment of Renal Diseases

Gluba-Brzózka¹,

Franczyk

Olszewski

et al. 2017

IJMS

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The prevalence of renal diseases is rising and reaching 5–15% of the adult population. Renal damage is associated with disturbances of body homeostasis and the loss of equilibrium between exogenous and endogenous elements including drugs and metabolites. Studies indicate that renal diseases are influenced not only by environmental but also by genetic factors. In some cases the disease is caused by mutation in a single gene and at that time severity depends on the presence of one or two mutated alleles. In other cases, renal disease is associated with the presence of alteration within a gene or genes, but environmental factors are also necessary for the development of disease. Therefore, it seems that the analysis of genetic aspects should be a natural component of clinical and experimental studies. The goal of personalized medicine is to determine the right drug, for the right patient, at the right time. Whole-genome examinations may help to change the approach to the disease and the patient resulting in the creation of “personalized medicine” with new diagnostic and treatment strategies designed on the basis of genetic background of each individual. The identification of high-risk patients in pharmacogenomics analyses will help to avoid many unwarranted side effects while optimizing treatment efficacy for individual patients. Personalized therapies for kidney diseases are still at the preliminary stage mainly due to high costs of such analyses and the complex nature of human genome. This review will focus on several areas of interest: renal disease pathogenesis, diagnosis, treatment, rate of progression and the prediction of prognosis.

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Tacrolimus

Abstract: Tacrolimus is an important therapeutic option for the optimal individualisation of immunosuppressive therapy in transplant recipients.

Cited by 269 publications

References 292 publications

Pharmacodynamic Parameters of Immunosuppressive Drugs Are Not Correlated with Age, Duration of Dialysis, Percentage of Lymphocytes or Lymphocyte Stimulation Index in Renal Transplant Recipients

Pharmacodynamic Parameters of Immunosuppressive Drugs Are Not Correlated with Age, Duration of Dialysis, Percentage of Lymphocytes or Lymphocyte Stimulation Index in Renal Transplant Recipients

BMP type II receptor as a therapeutic target in pulmonary arterial hypertension

Personalized Medicine: New Perspectives for the Diagnosis and the Treatment of Renal Diseases

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