Background: A prolonged-release formulation of tacrolimus for once-daily administration (Tacrolimus QD) has been developed to offer potential improvements in patient adherence. This study compared the pharmacokinetics (PK) of tacrolimus in stable kidney transplant recipients before and after conversion from twice-daily tacrolimus (Tacrolimus BID) to Tacrolimus QD.
Methods: This was an open-label, multicenter replicate design study in stable adult kidney transplant recipients (≥6 months posttransplantation) maintained on Tacrolimus BID. Patients underwent four sequential 14-day treatment periods of alternating Tacrolimus BID and QD (mg:mg conversion). Four 24-hour PK profiles were collected, one on the last day of each treatment period. Adverse events were also reported.
Results: A total of 60 of 69 patients completed all 4 PK profiles. Steady-state tacrolimus area under the curve from 0 to 24 hours and Cmin were comparable for both formulations, with treatment ratio means (90% confidence intervals) of 92.9% (89.8%-96.0%) and 90.9% (87.3%-94.6%), respectively (acceptance interval: 80%-125%). Both formulations were well tolerated, with renal function remaining stable over the 8-week period. There was a good correlation between area under the curve from 0 to 24 hours and Cmin for Tacrolimus QD and BID (r = 0.88 and 0.82, respectively). The relationship between these two parameters was also similar.
Conclusions: The results of this study provide evidence for safe conversion from Tacrolimus BID to QD with appropriate trough concentration monitoring.