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Population pharmacokinetics of tacrolimus in pediatric refractory nephrotic syndrome and a summary of other pediatric disease models

  • Authors:
    • Dongdong Wang
    • Jinmiao Lu
    • Qin Li
    • Zhiping Li

  • View Affiliations

  • Published online on: March 27, 2019     https://doi.org/10.3892/etm.2019.7446
  • Pages: 4023-4031

  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Different tacrolimus (TAC) population pharmacokinetic (PPK) models have been established in various pediatric disease populations. However, a TAC PPK model for pediatric refractory nephrotic syndrome (PRNS) has not been well characterized. The current study aimed to establish a TAC PPK model in Chinese PRNS and provide a summary of previous literature concerning TAC PPK models in different pediatric diseases. A total of 147 TAC conventional therapeutic drug monitoring (TDM) data from multiple blood samples obtained from 65 Chinese patients with PRNS were characterized using nonlinear mixed‑effects modeling. The impacts of demographic features, biological characteristics and drug combination were evaluated. Model validation was assessed using the bootstrap method. A one‑compartment model with first‑order absorption and elimination was determined to be the most suitable model for TDM data in PRNS. The absorption rate constant (Ka) was set at 4.48 h‑1. The typical values of apparent oral clearance (CL/F) and apparent volume of distribution (V/F) in the final model were 5.46 l/h and 57.1 l, respectively. The inter‑individual variability of CL/F and V/F were 22.2 and 0.2%, respectively. The PPK equation for TAC was: CL/F = 5.46 x exponential function (EXP)(0.0323 x age) x EXP(‑0.359 x cystatin‑C) x EXP(0.148 x daily dose of TAC). No significant effects of covariates on V/F were observed. In conclusion, the current study developed and validated the first TAC PPK model for patients with PRNS. The study also provided a summary of previous literature concerning other TAC PPK models in different pediatric diseases.
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May-2019
Volume 17 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Wang D, Lu J, Li Q and Li Z: Population pharmacokinetics of tacrolimus in pediatric refractory nephrotic syndrome and a summary of other pediatric disease models. Exp Ther Med 17: 4023-4031, 2019.
APA
Wang, D., Lu, J., Li, Q., & Li, Z. (2019). Population pharmacokinetics of tacrolimus in pediatric refractory nephrotic syndrome and a summary of other pediatric disease models. Experimental and Therapeutic Medicine, 17, 4023-4031. https://doi.org/10.3892/etm.2019.7446
MLA
Wang, D., Lu, J., Li, Q., Li, Z."Population pharmacokinetics of tacrolimus in pediatric refractory nephrotic syndrome and a summary of other pediatric disease models". Experimental and Therapeutic Medicine 17.5 (2019): 4023-4031.
Chicago
Wang, D., Lu, J., Li, Q., Li, Z."Population pharmacokinetics of tacrolimus in pediatric refractory nephrotic syndrome and a summary of other pediatric disease models". Experimental and Therapeutic Medicine 17, no. 5 (2019): 4023-4031. https://doi.org/10.3892/etm.2019.7446