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The impact of sulfonylureas on tacrolimus apparent clearance revealed by a population pharmacokinetics analysis in Chinese adult liver-transplant patients.
Ther Drug Monit. 2012 Apr; 34(2):126-33.TD

Abstract

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 (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.

Authors+Show Affiliations

Department of Pharmacy, Shanghai pulmonary Hospital, Tongji University School of Medicine, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22377746

Citation

Zhang, Xiao-qing, et al. "The Impact of Sulfonylureas On Tacrolimus Apparent Clearance Revealed By a Population Pharmacokinetics Analysis in Chinese Adult Liver-transplant Patients." Therapeutic Drug Monitoring, vol. 34, no. 2, 2012, pp. 126-33.
Zhang XQ, Wang ZW, Fan JW, et al. The impact of sulfonylureas on tacrolimus apparent clearance revealed by a population pharmacokinetics analysis in Chinese adult liver-transplant patients. Ther Drug Monit. 2012;34(2):126-33.
Zhang, X. Q., Wang, Z. W., Fan, J. W., Li, Y. P., Jiao, Z., Gao, J. W., Peng, Z. H., & Liu, G. L. (2012). The impact of sulfonylureas on tacrolimus apparent clearance revealed by a population pharmacokinetics analysis in Chinese adult liver-transplant patients. Therapeutic Drug Monitoring, 34(2), 126-33. https://doi.org/10.1097/FTD.0b013e31824a67eb
Zhang XQ, et al. The Impact of Sulfonylureas On Tacrolimus Apparent Clearance Revealed By a Population Pharmacokinetics Analysis in Chinese Adult Liver-transplant Patients. Ther Drug Monit. 2012;34(2):126-33. PubMed PMID: 22377746.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The impact of sulfonylureas on tacrolimus apparent clearance revealed by a population pharmacokinetics analysis in Chinese adult liver-transplant patients. AU - Zhang,Xiao-qing, AU - Wang,Zhao-wen, AU - Fan,Jun-wei, AU - Li,Yu-ping, AU - Jiao,Zheng, AU - Gao,Jun-wei, AU - Peng,Zhi-hai, AU - Liu,Gao-lin, PY - 2012/3/2/entrez PY - 2012/3/2/pubmed PY - 2012/7/12/medline SP - 126 EP - 33 JF - Therapeutic drug monitoring JO - Ther Drug Monit VL - 34 IS - 2 N2 - 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 (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. SN - 1536-3694 UR - https://www.unboundmedicine.com/medline/citation/22377746/The_impact_of_sulfonylureas_on_tacrolimus_apparent_clearance_revealed_by_a_population_pharmacokinetics_analysis_in_Chinese_adult_liver_transplant_patients_ L2 - https://doi.org/10.1097/FTD.0b013e31824a67eb DB - PRIME DP - Unbound Medicine ER -