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. DATA SOURCES: 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. STUDY SELECTION: Open and controlled clinical and animal trials were reviewed in evaluating the pharmacology, pharmacokinetics, and adverse effects of tacrolimus. DATA EXTRACTION: Data from animal and human studies published in the English literature were evaluated. DATA SYNTHESIS: 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.

This article has been cited by other articles:

				X.-S. Miao, P. Song, R. E. Savage, C. Zhong, R.-Y. Yang, D. Kizer, H. Wu, E. Volckova, M. A. Ashwell, J. G. Supko, et al. Identification of the in Vitro Metabolites of 3,4-Dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione (ARQ 501; {beta}-Lapachone) in Whole Blood Drug Metab. Dispos., April 1, 2008; 36(4): 641 - 648. [Abstract] [Full Text] [PDF]

				L. A. Eckstein, K. R. Van Quill, S. K. Bui, M. S. Uusitalo, and J. M. O'Brien Cyclosporin A Inhibits Calcineurin/Nuclear Factor of Activated T-Cells Signaling and Induces Apoptosis in Retinoblastoma Cells Invest. Ophthalmol. Vis. Sci., March 1, 2005; 46(3): 782 - 790. [Abstract] [Full Text] [PDF]

				H. V. Torocsik, R. G. Curless, J. Post, A. G. Tzakis, and L. Pearse FK506-induced leukoencephalopathy in children with organ transplants Neurology, April 1, 1999; 52(7): 1497 - 1497. [Abstract] [Full Text]

				A. Reis, T. Reinhard, R. Sundmacher, C. Braunstein, and E. Godehardt Effect of mycophenolate mofetil, cyclosporin A, and both in combination in a murine corneal graft rejection model Br. J. Ophthalmol., June 1, 1998; 82(6): 700 - 703. [Abstract] [Full Text]

				V. AGGARWAL, M D WILLIAMS, and S V BEATH Gastrointestinal problems in the immunosuppressed patient Arch. Dis. Child., January 1, 1998; 78(1): 5 - 8. [Full Text]

				P. H. Hinderling Red Blood Cells: A Neglected Compartment in Pharmacokinetics and Pharmacodynamics Pharmacol. Rev., September 1, 1997; 49(3): 279 - 295. [Abstract] [Full Text] [PDF]