Therapeutic Drug Monitoring

Skip Navigation LinksHome > April 2012 - Volume 34 - Issue 2 > The Impact of Sulfonylureas on Tacrolimus Apparent Clearance...
Therapeutic Drug Monitoring:
doi: 10.1097/FTD.0b013e31824a67eb
Original Article

The Impact of Sulfonylureas on Tacrolimus Apparent Clearance Revealed by a Population Pharmacokinetics Analysis in Chinese Adult Liver-Transplant Patients

Zhang, Xiao-qing PhD*; Wang, Zhao-wen MD, PhD; Fan, Jun-wei MD, PhD; Li, Yu-ping MD*; Jiao, Zheng PhD; Gao, Jun-wei PhD§; Peng, Zhi-hai MD, PhD; Liu, Gao-Lin PhD

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Aims: The aims of this study were to determine the population pharmacokinetics of tacrolimus in Chinese adult liver-transplant recipients and to identify factors that may account for this variability.

Methods: Tacrolimus dose and blood concentrations, along with clinical data, were collected retrospectively from 262 liver-transplant recipients. Data were analyzed using a nonlinear mixed-effects modeling method. A 1-compartment model with first-order absorption and elimination was selected as the base model. The influence of the following parameters were explored: (1) demographic characteristics, (2) biochemical and hematological laboratory test results, (3) surgery parameters, and (4) commonly used comedications.

Results: The typical values (interindividual variability percent coefficient of variation) for apparent clearance (CL/F) and apparent volume of distribution (V/F) were 20.9 L h−1 (23.8%) and 808 l (70.4%), respectively. The residual variability was 33.6%. Finally, the 4 covariates that showed a strong correlation with CL/F in this study were daily dose, hematocrit, total plasma protein, and the coadministration of sulfonylureas. CL/F was reduced significantly with sulfonylureas cotherapy, higher hematocrit levels, and elevated total protein. Moreover, CL/F increased nonlinearly with larger daily doses of tacrolimus.

Conclusions: Concurrent therapy with sulfonylureas influenced tacrolimus CL/F in liver transplantation patients. These results and model will help clinicians to optimize tacrolimus regimens in Chinese liver transplantation patients.

© 2012 Lippincott Williams & Wilkins, Inc.


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