CIRCADIAN VARIATION OF TACROLIMUS DISPOSITION IN LIVER ALLOGRAFT RECIPIENTS1

Abstract

The aim of this study was to characterize the circadian variation of oral tacrolimus disposition in 8 stable liver allograft recipients. In the steady state, a total of 23 blood samples was taken before and after tacrolimus administration during a 24-hr period and the pharmacokinetic parameters were compared. The area under the curve (AUC) of tacrolimus after the morning dose was significantly larger than after the evening dose(211±43 ng·hr/ml [morning] vs. 179±45 ng·hr/ml[evening], P=0.02). The time to peak (Tmax) was significantly shorter after the morning dose than after the evening dose(1.6±0.7 hr [morning] vs. 2.9±0.6 hr [evening],P=0.002). The peak (Cmax) was significantly higher after the morning dose than after the evening dose (32.2±10.2 ng/ml [morning] vs. 19.1±4.3 ng/ml [evening], P=0.003). However, the trough (Cmin) was not significantly different between the morning dose and the evening dose (13.1±3.9 ng/ml [morning] vs. 13.3±4.4 ng/ml[evening], P=0.4). This study demonstrated that tacrolimus disposition in liver transplant patients was determined by administration time.