Tacrolimus

Scott, Lesley J.; McKeage, Kate; Keam, Susan J.; Plosker, Greg L.

doi:10.2165/00003495-200363120-00006

Cited by 373 publications

(74 citation statements)

References 204 publications

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“…[23][24][25][26] In addition, inhibition of calcineurin blocks dephosphorylation of the transcription factor NF-AT in the cytoplasm, which is required for nuclear translocation and the NF-AT-regulated expression of cytokine genes such as IL-2. 27,28) The differences between the mechanisms of FR276457 and tacrolimus might be the reason that additive or synergistic effects are seen when the two are coadministered.…”

Section: Discussionmentioning

confidence: 99%

Effect of a New Immunosuppressant Histon Deacetylase (HDAC) Inhibitor FR276457 in a Rat Cardiac Transplant Model

Kinugasa

Yamada²,

Noto

et al. 2008

Biological & Pharmaceutical Bulletin

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Histone deacetylase (HDAC) is a known modulator of gene transcription, and the immunosuppressive activity of HDAC inhibitors has been demonstrated in recent several reports. In this study, the HDAC inhibitor FR276457, a hydroxamic derivative, was found to have a similar inhibitory effect on all mammalian HDACs tested, but no isozyme selectivity. Both FR276457 and tacrolimus exerted an immunosuppressive effect on in vitro rat splenocyte proliferation stimulated with Concanavalin A. Next, the effect of FR276457 on allograft rejection when administered either as a monotherapy or in combination with tacrolimus was investigated in a rat heterotopic cardiac transplant model. Orally administered FR276457 prolonged the median survival times (MST) of the transplanted grafts in the vehicle group from 6 d to 17 or 21 d at doses of 20 or 40 mg/kg, respectively. Histopathological analysis showed the structures of the myocardium were not affected, but interstitial cellular infiltration could not be suppressed completely. Tacrolimus (0.032 mg/kg) prolonged allograft MST to 16 d. FR276457, when combined with tacrolimus, prevented allograft rejection at a dose lower than that of the monotherapy. The combination dose prolonged the MST in the groups treated with 10 and 20 mg/kg to Ͼ28 d, and cellular infiltration was suppressed completely. In conclusion, this study demonstrated that the oral administration of HDAC inhibitor FR276457 can prevent allograft rejection as a monotherapy, and has additive or synergistic effects when combined with tacrolimus.

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Section: Discussionmentioning

confidence: 99%

Effect of a New Immunosuppressant Histon Deacetylase (HDAC) Inhibitor FR276457 in a Rat Cardiac Transplant Model

Kinugasa

Yamada²,

Noto

et al. 2008

Biological & Pharmaceutical Bulletin

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“…24) However, these adverse effects were thought to be caused by long-term use. The minimal lethal dose of tacrolimus in rats was reported at 18 mg/kg for intravenous dosing (18-fold higher dose than that used in this study), 25) and no unusual clinical sign or gross pathological abnormality was observed at 2 weeks after MCA occlusion in our previous study.…”

Section: Fig 3 Immunostaining For Granulocytes and Cd61 Positive Plmentioning

confidence: 99%

Tacrolimus (FK506) Limits Accumulation of Granulocytes and Platelets and Protects against Brain Damage after Transient Focal Cerebral Ischemia in Rat

Noto

Furuichi

Ishiye

et al. 2007

Biological & Pharmaceutical Bulletin

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Cerebral ischemia is one of the most frequent causes of disability and death in later life. The primary aim of therapeutic intervention for cerebral ischemia is to reduce the volume of brain damage and thus to minimize the neurological impairment. Because neuronal degeneration after cerebral ischemia can progress rapidly and is often irreversible, the benefit of effective pharmacological intervention is quite limited at present. The only medication proven to be effective and widely used at the acute stage of human stroke is tissue plasminogen activator (tPA). 1)

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“…As a key immunosuppressive drug, MPA in combination with calcineurin inhibitors (CNIs) and steroids has been used effectively in renal transplant recipients [2,3,4]. Because of variability in the dose-concentration relationship, MPA exposure should be measured and doses should be adjusted accordingly to achieve optimal clinical outcomes [5].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Mycophenolic Acid Exposure Using a Limited Sampling Strategy in Renal Transplant Recipients

Liu²,

Huang³

et al. 2013

Am J Nephrol

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Background/Aims: While there are drug exposure equation models based on limited sampling times for mycophenolate mofetil (MMF), there are few for enteric-coated mycophenolate sodium (EC-MPS), and none that studied Chinese individuals. Our objective is to generate the optimal model equations for estimation of the mycophenolic acid (MPA) area under the plasma concentration-time curve from 0 to 12 h (MPA-AUC_0-12h) with a limited sampling strategy (LSS) for renal transplant recipients receiving EC-MPS. Methods: The pharmacokinetics in 31 Chinese renal allograft recipients treated with EC-MPS in combination with tacrolimus and steroids were determined. The model equations were generated by multiple stepwise regression analysis for estimation of the MPA-AUC. Results: A total of 31 patients with an average age and weight of 37.58 ± 10.9 years and 60.9 ± 10.7 kg, respectively, were included. Mean serum creatinine and glomerular filtration rate were 112.2 ± 17.7 μmol/l and 65.6 ± 14.6 ml/min, respectively. The mean values of AUC_0-12h, pre-dose MPA trough concentration (C₀), maximum concentrations (C_max), and time to reach C_max (T_max) were 61.17 ± 26.39 mg·h/l (range 22.9-123.0 mg·h/l), 4.98 ± 4.65 mg/l (range 0.13-20.04 mg/l), 17.54 ± 10.67 mg/l (range 4.08-42.36 mg/l), and 5.0 ± 2.6 h (range 1.0-10.5 h), respectively. The best predictive equation for estimation of MPA-AUC_0-12h was -3.63 + 8.35 × C₄ + 17.04 × C₇ + 13.74 × C₁₂ (r² = 0.7491), prediction bias (PE%) was 20.9 ± 20.37, and prediction precision (APE%) was 3.66 ± 29.20. Conclusions: This model provides an effective approach for estimation of full MPA-AUC_0-12h in Chinese adult renal allograft recipients treated with EC-MPS and tacrolimus.

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Tacrolimus

Cited by 373 publications

References 204 publications

Effect of a New Immunosuppressant Histon Deacetylase (HDAC) Inhibitor FR276457 in a Rat Cardiac Transplant Model

Effect of a New Immunosuppressant Histon Deacetylase (HDAC) Inhibitor FR276457 in a Rat Cardiac Transplant Model

Tacrolimus (FK506) Limits Accumulation of Granulocytes and Platelets and Protects against Brain Damage after Transient Focal Cerebral Ischemia in Rat

Evaluation of Mycophenolic Acid Exposure Using a Limited Sampling Strategy in Renal Transplant Recipients

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