Circadian variation of tacrolimus disposition in liver allograft recipients.
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 x hr/ml [morning] vs. 179+/-45 ng x 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.
Min
D I
DI
College of Pharmacy, University of Iowa, Iowa City 52242, USA.
Chen
H Y
HY
Fabrega
A
A
Ukah
F O
FO
Wu
Y M
YM
Corwin
C
C
Ashton
M K
MK
Martin
M
M
D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000009:adverse effects / Q000493:pharmacokinetics*
D016559:Tacrolimus