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

David I. Min, Hsiang Yin Chen, Myung Koo Lee, Kay Ashton, Maureen F. Martin

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 (T(max)) 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 (C(max)) 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 trough concentration (C(min)) was not significantly different between doses. Endothelin-1 concentrations followed the same pattern as tacrolimus, with AUC and C(max) 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; C(max) 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.

Original languageEnglish
Pages (from-to)457-463
Number of pages7
JournalPharmacotherapy
Volume17
Issue number3
Publication statusPublished - May 1997
Externally publishedYes

Fingerprint

Tacrolimus
Endothelin-1
Allografts
Liver
Area Under Curve
Immunoenzyme Techniques
Cross-Over Studies
Pharmacokinetics
Transplants
Research

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Time-dependent disposition of tacrolimus and its effect on endothelin-1 in liver allograft recipients. / Min, David I.; Chen, Hsiang Yin; Lee, Myung Koo; Ashton, Kay; Martin, Maureen F.

In: Pharmacotherapy, Vol. 17, No. 3, 05.1997, p. 457-463.

Research output: Contribution to journalArticle

Min, David I. ; Chen, Hsiang Yin ; Lee, Myung Koo ; Ashton, Kay ; Martin, Maureen F. / Time-dependent disposition of tacrolimus and its effect on endothelin-1 in liver allograft recipients. In: Pharmacotherapy. 1997 ; Vol. 17, No. 3. pp. 457-463.
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title = "Time-dependent disposition of tacrolimus and its effect on endothelin-1 in liver allograft recipients",
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 (T(max)) 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 (C(max)) 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 trough concentration (C(min)) was not significantly different between doses. Endothelin-1 concentrations followed the same pattern as tacrolimus, with AUC and C(max) 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; C(max) 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.",
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T1 - Time-dependent disposition of tacrolimus and its effect on endothelin-1 in liver allograft recipients

AU - Min, David I.

AU - Chen, Hsiang Yin

AU - Lee, Myung Koo

AU - Ashton, Kay

AU - Martin, Maureen F.

PY - 1997/5

Y1 - 1997/5

N2 - 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 (T(max)) 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 (C(max)) 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 trough concentration (C(min)) was not significantly different between doses. Endothelin-1 concentrations followed the same pattern as tacrolimus, with AUC and C(max) 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; C(max) 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.

AB - 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 (T(max)) 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 (C(max)) 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 trough concentration (C(min)) was not significantly different between doses. Endothelin-1 concentrations followed the same pattern as tacrolimus, with AUC and C(max) 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; C(max) 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.

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