Tacrolimus, a new immunosuppressant--a review of the literature.
OBJECTIVE
To review the clinical pharmacology, pharmacokinetics, adverse effects, therapeutic uses, and current status of tacrolimus.


METHODS
Data from scientific literature were identified by a MEDLINE search. The data were extracted, evaluated, and summarized for presentation. Experiences from studies evaluating tacrolimus in the form of articles, abstracts, letters to the editor, or proceedings were considered for inclusion.


METHODS
Open and controlled clinical and animal trials were reviewed in evaluating the pharmacology, pharmacokinetics, and adverse effects of tacrolimus.


METHODS
Data from animal and human studies published in the English literature were evaluated.


RESULTS
Tacrolimus is an 822-kDa macrolide antibiotic that has potent immunosuppressive properties. The mechanism of action is similar to that of cyclosporine in that it ultimately blocks the production of interleukin 2, thereby inhibiting further T-lymphocyte proliferation. Tacrolimus is metabolized solely in the liver and the metabolites are primarily excreted in the bile. The elimination half-life of tacrolimus is approximately 8.5 h, and is prolonged in hepatic dysfunction. Tacrolimus has shown efficacy in the prophylaxis of allograft rejection in both animals and human clinical trials, and has been used effectively to rescue patients who have exhibited refractory rejection failing cyclosporine prophylaxis. Adverse effects requiring tacrolimus dosage adjustment include nephrotoxicity, neurotoxicity, alterations in glucose metabolism, and infection or susceptibility to malignancy.


CONCLUSIONS
To date, trials comparing tacrolimus with cyclosporine are not available in the literature; however, tacrolimus appears to be useful in rescuing grafts, particularly liver grafts that fail cyclosporine-based immunosuppression. Direct comparisons with cyclosporine are needed to define the role of tacrolimus as primary transplant therapy.
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Department of Pharmaceutical Services, Emory University Hospital, Atlanta, GA.
D000042:Absorption; D000818:Animals; D002986:Clinical Trials as Topic; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D016031:Liver Transplantation; D016559:Tacrolimus / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
D016559:Tacrolimus