Tacrolimus Intrapatient Variability After Switching From Immediate or Prolonged-Release to Extended-Release Formulation, After an Organ Transplantation
Arnaud Del BelloClotilde GaibleNathalie LongluneAnne‐Laure HebralLaure EspositoPeggy GandiaNassim Kamar
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Background and Purpose: Several formulations of tacrolimus are available, but evidence of the benefit of changing to the most recent formulations is lacking. Tacrolimus intra-patient variability (tacrolimus IPV) is an emerging risk factor associated with poor graft outcomes after solid organ transplantations. Here, we examined the modifications of tacrolimus IPV after switching to a different formulation of tacrolimus. Experimental Approach: We identified 353 solid organ transplant recipients that were switched in our center from immediate-release (IR-tacrolimus) or prolonged-release tacrolimus (PR-tacrolimus) to extended-release, LCP-tacrolimus (LCP-tacrolimus). Among them, 54 patients underwent at least 3 available tacrolimus blood concentrations before and after the switch, allowing us to investigate tacrolimus IPV. Key Results: The switch was considered as a safe procedure since only four of the 353 patients presented a graft rejection after the switch, and no patient was hospitalized for tacrolimus overdose. The tacrolimus IPV estimated by the coefficient of variation (CV-IPV) was stable before and after the switch to LCP-tacrolimus (CV-IPV: 29.0% (IQR 25–75 (15.5; 38.5) before and 24.0% (15.8; 36.5) after the switch, p = 0.65). Conclusion and Implications : Switching from IR- or PR-tacrolimus to LCP-tacrolimus is a safe procedure. However, the CV-tacrolimus IPV was not impacted by the change of formulation.This article is an attempt made by the author to discuss the various aspects of transplantation of human organ and its legal features. Human organ and tissue transplantation was started in India in 1962. Earlier, the human organ transplant was unfettered, and human organ trafficking was rampant in the society. The parliament of India first drafted The Transplantation of Human Organ Act governing the transplantation which was passed in 1994. This act has been subsequently amended in 2011, and new rules came into force in 2014. This research paper discusses the significant mechanism of the act and spotlights on what all medical practitioners involved in transplant should know about the legal aspects of transplantation.
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Abstract Transplant rejection is the key problem in organ transplantation and, in clinic, immunosuppressive agents such as tacrolimus are directly administered to the recipients after surgery for T‐cell inhibition. However, direct administration of tacrolimus may bring severe side effects to the recipients. Herein, by rational design of two hydrogelators NapPhePheGluTyrOH ( 1 ) and Nap d ‐Phe d PheGluTyrOH ( 2 ), a facile method of immune responsive release of tacrolimus is developed from their hydrogels to overcome organ transplantation rejection. Upon incubation with protein tyrosine kinase, which is activated in T cells after organ transplantation, the tacrolimus‐encapsulating Gel 1 or Gel 2 is disassembled to release tacrolimus. Cell experiments show that both Gel 1 and Gel 2 have better inhibition effect on the activated T cells than free drug tacrolimus. Liver transplantation experiments indicate that, after 7 days of treatment of same dose tacrolimus, the recipient rats in the Gel 2 group show significantly extended median survival time of 22 days while the recipients treated with conventional tacrolimus medication have a median survival time of 13 days. It is expected herein that this “smart” facile method of immune responsive release of tacrolimus can be applied to overcome organ transplantation rejection in clinic in the near future.
Graft rejection
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In their book Spare Parts, published in 1992, Fox and Swazey criticized various aspects of organ transplantation, including the routinization of the procedure, ignorance regarding its inherent uncertainties, and the ethos of transplant professionals. Using this work as a frame of reference, we analyzed articles on organ transplantation published in internal medicine and transplantation journals between 1995 and 2008 to see whether Fox and Swazey's critiques of organ transplantation were still relevant.
Philosophy of medicine
Economic shortage
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Background and Purpose: Several formulations of tacrolimus are available, but evidence of the benefit of changing to the most recent formulations is lacking. Tacrolimus intra-patient variability (tacrolimus IPV) is an emerging risk factor associated with poor graft outcomes after solid organ transplantations. Here, we examined the modifications of tacrolimus IPV after switching to a different formulation of tacrolimus. Experimental Approach: We identified 353 solid organ transplant recipients that were switched in our center from immediate-release (IR-tacrolimus) or prolonged-release tacrolimus (PR-tacrolimus) to extended-release, LCP-tacrolimus (LCP-tacrolimus). Among them, 54 patients underwent at least 3 available tacrolimus blood concentrations before and after the switch, allowing us to investigate tacrolimus IPV. Key Results: The switch was considered as a safe procedure since only four of the 353 patients presented a graft rejection after the switch, and no patient was hospitalized for tacrolimus overdose. The tacrolimus IPV estimated by the coefficient of variation (CV-IPV) was stable before and after the switch to LCP-tacrolimus (CV-IPV: 29.0% (IQR 25–75 (15.5; 38.5) before and 24.0% (15.8; 36.5) after the switch, p = 0.65). Conclusion and Implications : Switching from IR- or PR-tacrolimus to LCP-tacrolimus is a safe procedure. However, the CV-tacrolimus IPV was not impacted by the change of formulation.
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Organ Transplantation and Replacement, edited by G. James Cerilli, is the first major comprehensive textbook on the art and science of organ transplantation in more than 15 years that has been sponsored and edited in the United States. Najarian and Simmons' now classicTransplantation, published in 1972, followed a period of tremendous growth in the immunology and art of transplantation. A new explosion of knowledge in the 1980s has made that classic work obsolete. This new text is thus a very timely and much needed work with primarily American contributors giving us their latest data and experiences in multiple organ transplantation, with additional information on the use of artificial organs in replacement therapy. While remaining quite prophetic, the editor himself surprisingly states that "Kidney transplantation therapy is still palliative" while maintaining that the "era of the biologic manipulation of the human recipient is just begining." He believes that mechanical organ
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Transplantation immunology is the basis of modern organ transplantation.The history of organ transplantation demonstrated that the progress of basic research of transplantation immunology played critical role in the success of clinical organ transplantation.Based on the discovery of microchimerism of long-surviving organ recipients,Early of 1990's Starzl proposed his “Two-way paradigm” of graft rejection,reflecting the rule and characters of the graft rejection in the condition of immunosuppress-based clinical organ transplantation.The proposal of Two-way paradigm is an important theoretical progress in the history of transplantation immunology,which will greatly impulse the advance on the induction of transplantation tolerance in clinic.
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Abstract There are around 10.000 people in Poland who have undergone an organ transplantation at some point in their lives. This procedure allowed those people to enjoy regained health and successfully return to normal life, with the previously assigned roles at work, in their family and in society. Despite the advances in transplantation, a half of the people waiting for this form of treatment would die, since there are no organs to be transplanted. This state of affairs is caused by the low awareness among the Polish society. Polish people have very low confidence in this treatment method. They lack a basic understanding of the essential medical and legal procedures defining the organization of organ transplantation. Health educators should address concerns that emerge in society and to present a positive image of transplantation, as a science saving people’s lives. Educating young people about organ transplantation, since their earliest days at school, provides a chance to shape a positive attitude towards the issues of organ transplantation. This article attempts to answer the following questions: what is health education, organ transplantation, and what are the goals of the health education programs promoting organ transplantation?
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