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Population pharmacokinetics and pharmacogenetics of tacrolimus in healthy Chinese volunteers.
Pharmacology. 2011; 88(5-6):288-94.P

Abstract

AIM

The aim of this study was to establish population pharmacokinetic models of tacrolimus in healthy Chinese volunteers.

METHODS

A total of 956 tacrolimus whole blood concentrations from 73 healthy volunteers were determined using ultraperformance liquid chromatography mass spectrometry/mass spectrometry. Population pharmacokinetic analyses were performed using NONMEM. The final population pharmacokinetic models were validated with bootstrap and visual predictive check. A number of covariates were analyzed, including CYP3A5 and ABCB1 polymorphism, demographic characteristics and hematological and biological indices.

RESULTS

The structural model was a two-compartment model with first-order absorption, and a lag time was fitted to the data. The typical population values of tacrolimus for the pharmacokinetic parameters of apparent clearance (CL/F), apparent distribution volume of the central compartment (V(2)/F), intercompartmental clearance (Q/F), apparent distribution volume of the peripheral compartment (V(3)/F), absorption rate (ka) and lag time (ALAG) were 27.7 l/h, 37.5 liters, 34.4 l/h, 357 liters, 0.795 h(-1) and 0.226 h, respectively. The interindividual variabilities of these parameters were 63.3, 62.0, 50.8, 52.3, 32.9 and 4.45%, respectively, and the intraindividual variability of observed concentrations was 14.9%. The covariates that were retained in the final models were CYP3A5 genotype on CL/F, and body surface area and red blood count on V(3)/F.

CONCLUSION

Population pharmacokinetic models of tacrolimus were developed in healthy volunteers. These results could provide a reference for individualized tacrolimus therapy in the clinical setting.

Authors+Show Affiliations

Department of Clinical Pharmacology, First Affiliated Hospital of Soochow University, Suzhou, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22075549

Citation

Xue, Ling, et al. "Population Pharmacokinetics and Pharmacogenetics of Tacrolimus in Healthy Chinese Volunteers." Pharmacology, vol. 88, no. 5-6, 2011, pp. 288-94.
Xue L, Zhang H, Ma S, et al. Population pharmacokinetics and pharmacogenetics of tacrolimus in healthy Chinese volunteers. Pharmacology. 2011;88(5-6):288-94.
Xue, L., Zhang, H., Ma, S., Rui, J. Z., & Miao, L. Y. (2011). Population pharmacokinetics and pharmacogenetics of tacrolimus in healthy Chinese volunteers. Pharmacology, 88(5-6), 288-94. https://doi.org/10.1159/000331856
Xue L, et al. Population Pharmacokinetics and Pharmacogenetics of Tacrolimus in Healthy Chinese Volunteers. Pharmacology. 2011;88(5-6):288-94. PubMed PMID: 22075549.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Population pharmacokinetics and pharmacogenetics of tacrolimus in healthy Chinese volunteers. AU - Xue,Ling, AU - Zhang,Hua, AU - Ma,Sheng, AU - Rui,Jian-Zhong, AU - Miao,Li-Yan, Y1 - 2011/11/10/ PY - 2011/04/08/received PY - 2011/07/18/accepted PY - 2011/11/15/entrez PY - 2011/11/15/pubmed PY - 2012/4/19/medline SP - 288 EP - 94 JF - Pharmacology JO - Pharmacology VL - 88 IS - 5-6 N2 - AIM: The aim of this study was to establish population pharmacokinetic models of tacrolimus in healthy Chinese volunteers. METHODS: A total of 956 tacrolimus whole blood concentrations from 73 healthy volunteers were determined using ultraperformance liquid chromatography mass spectrometry/mass spectrometry. Population pharmacokinetic analyses were performed using NONMEM. The final population pharmacokinetic models were validated with bootstrap and visual predictive check. A number of covariates were analyzed, including CYP3A5 and ABCB1 polymorphism, demographic characteristics and hematological and biological indices. RESULTS: The structural model was a two-compartment model with first-order absorption, and a lag time was fitted to the data. The typical population values of tacrolimus for the pharmacokinetic parameters of apparent clearance (CL/F), apparent distribution volume of the central compartment (V(2)/F), intercompartmental clearance (Q/F), apparent distribution volume of the peripheral compartment (V(3)/F), absorption rate (ka) and lag time (ALAG) were 27.7 l/h, 37.5 liters, 34.4 l/h, 357 liters, 0.795 h(-1) and 0.226 h, respectively. The interindividual variabilities of these parameters were 63.3, 62.0, 50.8, 52.3, 32.9 and 4.45%, respectively, and the intraindividual variability of observed concentrations was 14.9%. The covariates that were retained in the final models were CYP3A5 genotype on CL/F, and body surface area and red blood count on V(3)/F. CONCLUSION: Population pharmacokinetic models of tacrolimus were developed in healthy volunteers. These results could provide a reference for individualized tacrolimus therapy in the clinical setting. SN - 1423-0313 UR - https://www.unboundmedicine.com/medline/citation/22075549/Population_pharmacokinetics_and_pharmacogenetics_of_tacrolimus_in_healthy_Chinese_volunteers_ L2 - https://www.karger.com?DOI=10.1159/000331856 DB - PRIME DP - Unbound Medicine ER -