Effect of Breakfast on the Exposure of the Once-Daily Tacrolimus Formulation in Stable Kidney Transplant Recipients.

Abstract

The once-daily Tacrolimus formulation (Tac ONCE-DAILY) has to be taken on an empty stomach. This is inconvenient for patients and may hamper compliance. The influence of food intake on the exposure of Tac ONCE-DAILY is unknown in transplant recipients. We compared the pharmacokinetics (PKs) of Tac ONCE-DAILY in stable kidney transplant recipients under fasted and fed conditions. In an open-label, single-center, cross-over PK study, 27 stable kidney white transplant recipients (17 male, 10 female) treated with Tac ONCE-DAILY under fasted conditions were enrolled. Two 10-point 24-hour blood concentration time profiles [area under the blood concentration time curve from time 0 to 24 hours (AUC0-24)] were collected under steady state conditions. The primary objective was to investigate the effect of food on the PKs and relative bioavailability of Tac ONCE-DAILY. Twenty-seven stable renal transplant patients provided 1 AUC0-24 under fasted and fed conditions, respectively. AUC0-24, C24, and Cmax, were lower in the fed state and Tmax was 1 hour postponed. The 90% confidence interval ratio (fed: fasted) for AUC0-24 was 0.81-0.91 and for C24 0.82-0.92 (both P < 0.001). The majority (60%) had no significant change, but the change in AUC0-24 ranged from -38% to +29%. One trough level was below the target range after fed intake. When Tac ONCE-DAILY is ingested with standard continental breakfast, AUC0-24 and C24 decrease overall, with C24 in the therapeutic range in almost all patients. The convenient fed intake could promote therapy adherence. Given the possible significant change in exposure, we advise monitoring of the tacrolimus trough level 1 week after fed ingestion of Tac ONCE-DAILY.