DOI: 10.1002/ame2.70038
Long-term immunosuppression of rabbits through oral tacrolimus administration
Alexane Thibodeau1
Todd Galbraith1
Oumayma Hayouni1
Hélène T.Khuong2
François Berthod2
1.LOEX,Centre de Recherche du CHU de Québec-Université Laval,Hôpital de l'Enfant-Jésus,Québec City,Quebec,Canada2.LOEX,Centre de Recherche du CHU de Québec-Université Laval,Hôpital de l'Enfant-Jésus,Québec City,Quebec,Canada;Department of Surgery,Faculty of Medicine,Université Laval,Quebec City,Quebec,Canada
摘要：Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.However,determining the optimal dosage and route of administration to minimize toxicity while maintaining efficacy remains challenging.
Methods:In this study,we investigated the effect of orally administered tacrolimus in rabbits,with an aim to achieve a whole blood target trough level of 3-10 ng/mL,and looked at signs of tissue rejection after the transplantation of a human nerve conduit to repair a severed fibular nerve.An oral dosage range of 0.25-1.5 mg/kg/d was studied for up to 1 year in 63 New Zealand rabbits.
Results:We demonstrated the feasibility of long-term grafting in rabbits while maintaining safe immunosuppression,with side effects mainly limited to diarrhea.Customizing the administered dose proved crucial for graft efficacy and low toxicity,which translated into 100%individual survival.We suggest an oral tacrolimus dose of 1.0-1.5 mg/kg depending on individual heterogeneity and recommend to implement a close therapeutic drug monitoring in the rabbits to maintain a whole blood tacrolimus trough level within the range of 5-12 ng/mL,as levels below 5 ng/mL showed signs of inflammation in the graft.
Conclusion:The oral administration of tacrolimus enabled efficient immunosuppression of rabbits over a 1-year period without significant side effects or loss of animals.
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论文发表日期：2025-09-30
在线出版日期：2025-10-28（本平台首次上网日期，不代表文献的发表时间）
页数：10( 1700-1709 )
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