Circadian and time-dependent variability in tacrolimus pharmacokinetics

Tacrolimus (TAC) is considered a critical dose drug. The purpose of our study was to investigate circadian and time‐dependent changes in TAC pharmacokinetics over the first year after kidney transplantation. Pharmacokinetic (PK) studies were performed in 26 recipients of first living donor kidney transplants at day 7 after morning (a.m.) and evening (p.m.) doses of TAC. Additional serial PK studies were carried out in nine patients at month 6 (M6) and month 12 (M12). Blood samples were collected before 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 h after TAC administration. Demographics, TAC and adjunctive immunosuppressive doses, hematology, and biochemistry were recorded in each PK study. Mean age was 37 years, body mass index 23 kg/m2, 58% males, and 85% Caucasian. Higher AUC (231.4 vs. 220 ng·h/mL, P = 0.06) and Cmax (34.1 ± 12.6 vs. 24.4 ± 9.8 ng/mL, P