Abstract：
STUDY OBJECTIVE:To characterize a time-dependent disposition of oral tacrolimus and its relationship with plasma endothelin-1 concentrations. DESIGN:Randomized, crossover study. SETTING:Clinical research center of a university-affiliated hospital. PATIENTS:Twelve stable liver transplant recipients. INTERVENTIONS:In the steady state, 23 blood samples were taken from each patient before and after tacrolimus administration over 24 hours. MEASUREMENTS AND MAIN RESULTS: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. Endothelin-1 concentrations followed the same pattern as tacrolimus, with AUC and Cmax for the morning significantly higher than those for the evening dose of tacrolimus (AUC 13.8 +/- 3.7 pg.hr/ml, morning, and 11.0 +/- 3.5 pg.hr/ml, evening, p = 0.005; Cmax 2.4 +/- 1.1 pg/ml morning, and 1.5 +/- 0.6 pg/ml evening, p = 0.02). Tacrolimus levels did not correlate with endothelin-1 levels (r2 = 0.06, p = 0.001). CONCLUSIONS:Tacrolimus disposition in liver transplant patients is determined by time of administration. Plasma endothelin-1 concentrations follow the same pattern as blood tacrolimus concentrations.
journal_name
Pharmacotherapyjournal_title
Pharmacotherapyauthors
Min DI,Chen HY,Lee MK,Ashton K,Martin MFsubject
Has Abstractpub_date
1997-05-01 00:00:00pages
457-63issue
3eissn
0277-0008issn
1875-9114journal_volume
17pub_type
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