Abstract
TACROLIMUS (Tac) is a macrolide immunosuppressant that was isolated from Streptomyces tsukubaensis in 1984. Its mechanism of action closely resembles that of cyclosporine; that is, both bind to and inhibit the phosphatase activity of calcineurin. This results in the inhibition of gene transcription of IL-2, which is crucial for lymphocyte growth and proliferation. Experimental studies on different animal models have proven the effectiveness of Tac in the limitation of rejection in kidney, liver, and pancreas transplantation. Its use in clinical liver and kidney transplantation has gained wide acceptance and has allowed for a significant decrease in the number and severity of rejection episodes. More recently, the use of Tac has been extended into the field of thoracic organ transplantation both as rescue and as primary immunosuppression. Clinical studies have suggested that careful monitoring of blood concentrations is required for simultaneous avoidance of toxicity and graft rejection. Tac has a relatively narrow therapeutic index and the correlation of dose to blood concentration is poor as a result of interindividual variability in pharmacokinetic (PK) parameters and Tac cytochrome P450 3A4–mediated hepatic and intestinal metabolism. The PK of Tac has been well characterized in different kinds of transplants. Currently, little is known about PK of Tac in heart transplant (HTx) recipients and, in previous studies, PK parameters were considered only after the first doses. In the present study we more clearly define PK over a longer period of time.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call