Abstract

Tacrolimus, is a CNI marketed under the trade name Prograf[sup]®[/sup]; oral Prograf capsules are administered as a twice-daily dosing regimen. Poor compliance with dosing has been shown to be one of the factors associated with the incidence of transplant rejection and late graft loss and the likelihood for adherence is better with a once daily dosing regimen compared to that with twice daily dosing regimen. Advagraf has been developed as a once daily formulation of tacrolimus aimed at improving compliance with dosing and thereby decreasing the risk of late graft rejection and loss. Pharmacokinetics of Advagraf have been evaluated in stable adult kidney, liver and heart transplant recipients as well as de novo liver and kidney transplant recipients. In stable patients following conversion from Prograf to Advagraf on a 1:1 (mg:mg) total daily dose, systemic exposure to tacrolimus over 24 hour (AUC0-24) was similar. In de novo kidney and liver transplant patients AUC[sub]0-24[/sub] of tacrolimus for Advagraf on Day 1 was 30% and 50% lower respectively, when compared with that for Prograf at equivalent doses. By Day 4, systemic exposure is similar with both formulations. Efficacy and safety profile of Advagraf was comparable to Prograf with a patient follow up of up to 3 years. There was good correlation between AUC[sub]0-24[/sub] and trough level (C[sub]24[/sub]) of tacrolimus for Advagraf and the relationship between these two parameters is similar to that for Prograf, thus, therapy for both formulations can be optimised using the same therapeutic monitoring concept.

Keywords: Tacrolimus, Liver, Kidney Transplant