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The Population Pharmacokinetic Models of Tacrolimus in Chinese Adult Liver Transplantation Patients.

Zhu L, Wang H, Sun X, Rao W, Qu W, Zhang Y, Sun L - J Pharm (Cairo) (2014)

Bottom Line: The covariates retained in the final models were postoperative days (POD) and dosage per day (DOSE) on CL/F.Conclusion.These results could provide the interpretation of the outcome of pharmacokinetics modeling and the impact of covariate tested on individualized tacrolimus therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Tianjin First Central Hospital, Tianjin 300192, China.

ABSTRACT
Aim. The aim of this study was to establish population pharmacokinetic models of tacrolimus in Chinese adult liver transplantation patients. Methods. Tacrolimus dose and concentration data (n = 435) were obtained from 47 Chinese adult liver transplant recipients, and the data were analyzed using a nonlinear mixed-effect modeling (NONMEM) method. Results. The structural model was a two-compartment model with first-order absorption. 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), and absorption rate (k a ) were 11.2 L/h, 406 L, 57.3 L/h, 503 L, and 0.723 h(-1), respectively. The interindividual variabilities of these parameters were 16.2%, 163%, 19.7%, 199%, and 74.3%, respectively, and the intraindividual variability of observed concentration was 26.54%. The covariates retained in the final models were postoperative days (POD) and dosage per day (DOSE) on CL/F. Conclusion. Population pharmacokinetic models of tacrolimus were developed in Chinese adult liver transplant patients. These results could provide the interpretation of the outcome of pharmacokinetics modeling and the impact of covariate tested on individualized tacrolimus therapy.

No MeSH data available.


Fit plots of the final model: observations versus population predictions (a) and observations versus individual predictions (b). The bold solid lines represent the lines of unity.
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Related In: Results  -  Collection


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fig1: Fit plots of the final model: observations versus population predictions (a) and observations versus individual predictions (b). The bold solid lines represent the lines of unity.

Mentions: The goodness of fit of the final model is shown in Figure 1. The plot (a) showed observations versus population predictions and plot (b) showed observations versus individual predictions. The two plots, respectively, showed good individual and population predicted results.


The Population Pharmacokinetic Models of Tacrolimus in Chinese Adult Liver Transplantation Patients.

Zhu L, Wang H, Sun X, Rao W, Qu W, Zhang Y, Sun L - J Pharm (Cairo) (2014)

Fit plots of the final model: observations versus population predictions (a) and observations versus individual predictions (b). The bold solid lines represent the lines of unity.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4590802&req=5

fig1: Fit plots of the final model: observations versus population predictions (a) and observations versus individual predictions (b). The bold solid lines represent the lines of unity.
Mentions: The goodness of fit of the final model is shown in Figure 1. The plot (a) showed observations versus population predictions and plot (b) showed observations versus individual predictions. The two plots, respectively, showed good individual and population predicted results.

Bottom Line: The covariates retained in the final models were postoperative days (POD) and dosage per day (DOSE) on CL/F.Conclusion.These results could provide the interpretation of the outcome of pharmacokinetics modeling and the impact of covariate tested on individualized tacrolimus therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Tianjin First Central Hospital, Tianjin 300192, China.

ABSTRACT
Aim. The aim of this study was to establish population pharmacokinetic models of tacrolimus in Chinese adult liver transplantation patients. Methods. Tacrolimus dose and concentration data (n = 435) were obtained from 47 Chinese adult liver transplant recipients, and the data were analyzed using a nonlinear mixed-effect modeling (NONMEM) method. Results. The structural model was a two-compartment model with first-order absorption. 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), and absorption rate (k a ) were 11.2 L/h, 406 L, 57.3 L/h, 503 L, and 0.723 h(-1), respectively. The interindividual variabilities of these parameters were 16.2%, 163%, 19.7%, 199%, and 74.3%, respectively, and the intraindividual variability of observed concentration was 26.54%. The covariates retained in the final models were postoperative days (POD) and dosage per day (DOSE) on CL/F. Conclusion. Population pharmacokinetic models of tacrolimus were developed in Chinese adult liver transplant patients. These results could provide the interpretation of the outcome of pharmacokinetics modeling and the impact of covariate tested on individualized tacrolimus therapy.

No MeSH data available.