Conversion from twice-daily to once-daily tacrolimus does not reduce intrapatient variability in tacrolimus exposure

Intrapatient variability (IPV) in tacrolimus exposure is associated with renal allograft failure. The aim of this study was to investigate whether conversion from the twice-daily tacrolimus formulation (Tac-TD) to a once-daily formulation (Tac-OD) leads to a lower IPV in tacrolimus exposure.

Two hundred forty-seven stable renal transplant recipients were converted from Tac-TD to Tac-OD (Advagraf) on a 1:1-mg total daily dose basis. After conversion, patients were followed for 12 months and tacrolimus predose whole-blood concentrations (C0), serum creatinine, estimated glomerular filtration rate, and proteinuria were measured. These parameters were compared with those collected at all outpatient visits in the 12-month period (±3 months) before conversion (Tac-TD period). The IPV was calculated based on the dose-adjusted tacrolimus C0.

The Tac-OD formulation provided an excellent graft survival (100%), a low acute rejection rate (0.8%), and good tolerability. Renal function remained stable: estimated glomerular filtration rate 48 (16-90) versus 46 (12-90) mL/min (P = 0.15) before and after conversion, respectively. After conversion to Tac-OD, mean C0 was significantly lower, decreasing from 5.7 ± 1.5 to 5.0 ± 1.5 ng/mL, corresponding to a 12% reduction (P < 0.01). Both drugs had similar IPVs (Tac-TD: 17.3% ± 1.6% versus Tac-OD: 16.4% ± 1.6%, P = 0.31).

Although conversion from Tac-TD to Tac-OD significantly reduces tacrolimus exposure as measured by C0 and seems safe, it does not reduce IPV in tacrolimus exposure.