PMID: 9165550May 1, 1997Paper

Time-dependent disposition of tacrolimus and its effect on endothelin-1 in liver allograft recipients

Pharmacotherapy
D I MinM F Martin

Abstract

To characterize a time-dependent disposition of oral tacrolimus and its relationship with plasma endothelin-1 concentrations. Randomized, crossover study. Clinical research center of a university-affiliated hospital. Twelve stable liver transplant recipients. In the steady state, 23 blood samples were taken from each patient before and after tacrolimus administration over 24 hours. Whole blood samples for tacrolimus and plasma endothelin-1 were analyzed by enzyme immunoassay. The relationship of their concentrations and their pharmacokinetic parameters between morning and evening doses were compared. The area under the curve (AUC) of tacrolimus in the morning dose was significantly larger than that in the evening dose (219 +/- 54 ng.hr/ml and 188 +/- 57 ng.hr/ml, respectively, p = 0.004). The mean time to peak concentration (Tmax) was significantly shorter for the morning dose than for the evening dose (1.6 +/- 0.7 hrs and 3.5 +/- 2.9 hrs, respectively, p = 0.01). The mean peak concentration (Cmax) was significantly higher in the morning dose than in the evening dose (32.2 +/- 9.1 ng/ml and 21.6 +/- 8.3 ng/ml, respectively, p = 0.008). However, the mean through concentration (Cmin) was not significantly different between doses....Continue Reading

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