Tacrolimus in liver transplantation.

Tacrolimus has been in clinical use for ten years. It was launched in a hail of publicity following the successful treatment of cases with apparently irreversible rejection using conventional immunosuppressive therapies. Since that time, the overall experience with the drug has increased considerably. The purpose of this article is to review tacrolimus comprehensively, including evidence derived from major clinical trials, to enable the reader to become familiar with its clinical role, including a comparison with its main competitor, cyclosporin. Tacrolimus was discovered in 1984, it predominantly acts via inhibition of T-cell mediated immunity, and to a lesser extent B-cell humoral immunity. The agent was introduced into clinical medicine in 1989 and was soon shown to be a highly effective immunosuppressive agent, receiving approval in 1994 by the Food and Drug Administration (FDA) for primary immunosuppression in adult and paediatric liver transplantation. Tacrolimus has proved to be a major development in transplantation. Whilst the available data have been hindered to some extent by deficiencies of trial design in the major studies, there is still more comparative clinical data available for tacrolimus than for any of its predecessors. The overall balance of risk benefit is considered by many to be tipped in favour of tacrolimus; it is likely that with more long-term follow-up results becoming available in liver and other solid organ transplants, the benefits will appear clearer.