International journal of clinical pharmacology and therapeutics · 2022
Population pharmacokinetics and dose simulation of cyclosporine in Chinese children with nephrotic syndrome: Effects of weight and total cholesterol.
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Zhao Yiming, He Huan, Zang Yannan, Zhao Libo, Wang Xiaoling
Аннотация
OBJECTIVE: The existing cyclosporine (CsA) population pharmacokinetic (PPK) model does not apply well to children. The aim of the study was to establish a CsA PPK model for Chinese children with nephrotic syndrome (NS) and conduct a dosage simulation to provide drug-dosing guidance.
MATERIALS AND METHODS: A total of 311 drug monitoring data points were collected from 165 children. Blood samples were collected before dosing. Non-linear mixed-effects model was applied to develop the PPK model. Covariate analysis was applied to select candidate factors associated with pharmacokinetic (PK) parameters. A model-based simulation was then performed to estimate the optimal initial dose for different patient subgroups.
RESULTS: A one-compartment model with first-order absorption and elimination was chosen to describe the drug trajectory in vivo. The typical values for apparent clearance/absorption fraction (CL/F) and apparent volume of distribution/absorption fraction (V/F) were 40.1/h and 2.32 ×103L, respectively. The covariate analysis revealed that weight and total cholesterol were strongly associated with CL/F and V/F. Goodness-of-fit and model evaluation suggested that the proposed model was acceptable. A dosage regimen table was created for specific pediatric groups to facilitate clinical application.
CONCLUSION: A PPK model of CsA in Chinese pediatrics was successfully established, allowing the development of individualized dosing regimens for Chinese pediatric NS patients.
MATERIALS AND METHODS: A total of 311 drug monitoring data points were collected from 165 children. Blood samples were collected before dosing. Non-linear mixed-effects model was applied to develop the PPK model. Covariate analysis was applied to select candidate factors associated with pharmacokinetic (PK) parameters. A model-based simulation was then performed to estimate the optimal initial dose for different patient subgroups.
RESULTS: A one-compartment model with first-order absorption and elimination was chosen to describe the drug trajectory in vivo. The typical values for apparent clearance/absorption fraction (CL/F) and apparent volume of distribution/absorption fraction (V/F) were 40.1/h and 2.32 ×103L, respectively. The covariate analysis revealed that weight and total cholesterol were strongly associated with CL/F and V/F. Goodness-of-fit and model evaluation suggested that the proposed model was acceptable. A dosage regimen table was created for specific pediatric groups to facilitate clinical application.
CONCLUSION: A PPK model of CsA in Chinese pediatrics was successfully established, allowing the development of individualized dosing regimens for Chinese pediatric NS patients.