Modified Release Tacrolimus in De Novo Immunosuppression After Simultaneous Pancreas–Kidney Transplantation—A First Single-Center Experience

Schenker, Peter; Klein, Thomas; Krüger, Bernd; Claas, Silke; Wünsch, Andreas; Traska, T; Krämer, B. K.; Viebahn, Richard

doi:10.1016/j.transproceed.2009.06.114

Cited by 7 publications

(9 citation statements)

References 8 publications

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“…Modified-release tacrolimus with once daily administration has also been used safely. 3) There are no reports regarding the use of prolonged release formulations of tacrolimus in clinical practice, although some polymer-based formulations for longterm delivery of tacrolimus have been used in animal model studies. As has been previously reported, a single dose of the new type of tacrolimus with biodegradable microspheres could keep the plasma concentration steady for two weeks, suggesting that immunosuppressive activity could be achieved with the use of polymer-based formulations.…”

Section: Preparation Of High-payload Prolonged-release Biodegradablementioning

confidence: 99%

Preparation of High-Payload, Prolonged-Release Biodegradable Poly(lactic-<i>co</i>-glycolic acid)-Based Tacrolimus Microspheres Using the Single-Jet Electrospray Method

et al. 2016

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Tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres (TAC-PLGA-M) can be administered for the long-term survival of transplanted organs due to their immunosuppressive activity. The purpose of our study was to optimize the parameters of the electrospray method, and to prepare TAC-PLGA-M with a high payload and desirable release properties. TAC-PLGA-M were prepared using the electrospray method. In vitro characterization and evaluation were performed using scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy. Drug-loading efficiency was greater than 80% in all formulations with a maximum loading capacity of 16.81 0.37%. XRD and DSC studies suggested that the drug was incorporated in an amorphous state or was molecularly dispersed in the microspheres. The in vitro release study showed prolonged release patterns. TAC-PLGA-M with enhanced drug loading and prolonged-release patterns were successfully prepared using the electrospray method.Key words electrospray; microsphere; poly(lactic-co-glycolic acid); prolonged release; tacrolimus Tacrolimus (TAC), a potent immunosuppressant drug, is primarily used to increase the survival time of transplanted organs.1) The immunosuppressive activity of tacrolimus is mediated through the inhibition of calcineurin, which is a protein phosphatase found in the cytoplasm of T-cells, and the subsequent blockage of interleukin-2 production, leading to a decrease in T cell proliferation.2) In clinical practice, tacrolimus is administered as a twice-daily dosing regimen. Modified-release tacrolimus with once daily administration has also been used safely.3) There are no reports regarding the use of prolonged release formulations of tacrolimus in clinical practice, although some polymer-based formulations for longterm delivery of tacrolimus have been used in animal model studies. As has been previously reported, a single dose of the new type of tacrolimus with biodegradable microspheres could keep the plasma concentration steady for two weeks, suggesting that immunosuppressive activity could be achieved with the use of polymer-based formulations.4,5) Subcutaneous injection of tacrolimus pellets, which could give a plasma concentration within the desired therapeutic window, provided effective immunosuppression for more than three months in rat model studies.6) Likewise, tacrolimus-loaded biodegradable microspheres reportedly achieved sustained release over a long period, giving flat parallel concentration profiles for 10 d from the first day after a single subcutaneous administration in liver-transplanted rats. 7)Long-term controlled delivery of drugs has been accomplished by the use of biodegradable polymeric particulate systems.8) Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable polymer that undergoes hydrolysis in the body to produce two monomers: lactic acid and glycolic acid. The rate of degradation of PLGA and the release profile of drugs from PLGAbased formulations depend on the mole...

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Section: Preparation Of High-payload Prolonged-release Biodegradablementioning

confidence: 99%

Preparation of High-Payload, Prolonged-Release Biodegradable Poly(lactic-<i>co</i>-glycolic acid)-Based Tacrolimus Microspheres Using the Single-Jet Electrospray Method

et al. 2016

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“…32 One pancreas was lost 2 days postoperatively due to vascular graft thrombosis. Interestingly, drug levels declined in weeks 2-3, and the authors commented that patients sometimes required substantial doses and that drug levels responded slowly to dose changes.…”

Section: Simultaneous Pancreas Kidney Transplantationmentioning

confidence: 99%

“…They suggested that there might be a different pharmacokinetic profile in simultaneous pancreas kidney transplantation due to enteric drainage or improvements in gastroparesis. 32 This could be further dissected by analyzing pharmacokinetic data in patients with bladder drainage of exocrine secretions.…”

Section: Simultaneous Pancreas Kidney Transplantationmentioning

confidence: 99%

“…21 The efficacy and safety data from 14 additional observational studies are consistent with the randomized controlled trial data (Table 1). [19][20][21][22][23][24][25][26][27][28][29][30][31][32] Although the effect of TAC QD versus TAC BID on adherence in de novo transplantation has not been systematically tested, an industry-sponsored modeling analysis that extrapolated the effect on adherence, as well as outcomes from a literature review of other studies of twiceversus once-daily medication, suggested that, after 5 years, graft survival would be 6.1% higher in the TAC QD group, which would result in a cost saving of US $9,411 per patient over the 5 years. 33 TAC QD is a useful treatment option that may reduce pill burden in patients adapting to life after transplantation, but an advantage in terms of efficacy or safety has not been demonstrated.…”

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confidence: 99%

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Prevention of organ rejection in renal and liver transplantation with extended release tacrolimus

Reschen¹,

O’Callaghan²

2014

TRRM

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Tacrolimus is the key immunosuppressant used to prevent allograft rejection in kidney and liver transplant recipients. Despite the efficacy of tacrolimus and adjunctive immunosuppressants, a substantial number of patients experience episodes of acute rejection and late graft loss. Nonadherence is an etiological factor in both acute rejection and graft loss. In 2007, a prolonged release version of tacrolimus became available that allows once daily administration, thus halving the pill burden compared to the standard twice-daily tacrolimus. An increasing number of studies in de novo transplantation and in treatment conversion have evaluated the pharmacokinetic profile, efficacy, and safety of prolonged-release tacrolimus. We have reviewed the literature on the use of prolonged-release tacrolimus and hope that this will be of value in the design of protocols for transplant immunosuppression.

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“…A oncedaily oral preparation of tacrolimus (Tac-QD; Advagraf) has been introduced in clinical practice in recent years, and published reports suggest that it is as safe and effective as Tac-BD for renal as well as liver transplant recipients [2e4]. However, there is a paucity of data for simultaneous pancreas-kidney (SPK) transplant recipients, with only 1 small study suggesting that Tac-QD could be used in this patient group [5]. The perceived benefits of Tac-QD are a reduction in pill burden, which may translate into better patient compliance [6], thus minimizing the risk of graft dysfunction.…”

mentioning

confidence: 99%

Conversion From Twice-Daily to Once-Daily Tacrolimus in Simultaneous Pancreas-Kidney Transplant Patients

Falconer

Jansen

Oniscu

2014

Transplantation Proceedings

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Modified Release Tacrolimus in De Novo Immunosuppression After Simultaneous Pancreas–Kidney Transplantation—A First Single-Center Experience

Cited by 7 publications

References 8 publications

Preparation of High-Payload, Prolonged-Release Biodegradable Poly(lactic-<i>co</i>-glycolic acid)-Based Tacrolimus Microspheres Using the Single-Jet Electrospray Method

Preparation of High-Payload, Prolonged-Release Biodegradable Poly(lactic-<i>co</i>-glycolic acid)-Based Tacrolimus Microspheres Using the Single-Jet Electrospray Method

Prevention of organ rejection in renal and liver transplantation with extended release tacrolimus

Conversion From Twice-Daily to Once-Daily Tacrolimus in Simultaneous Pancreas-Kidney Transplant Patients

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