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Population pharmacokinetic and pharmacogenetics of imatinib in Chinese patients with chronic myeloid leukemia.
Pharmacogenomics 2019 Februrary 16
AIM: This study aimed to establish a population pharmacokinetic (PPK) model in Chinese patients with chronic myeloid leukemia, and to quantify the effects of pharmacogenetics on pharmacokinetic parameters of imatinib.
METHODS: A total of 229 plasma concentrations from 170 patients were analyzed. Nonlinear mixed effect model was used to establish the PPK model.
RESULTS: A one-compartment model with first-order absorption and first-order elimination adequately describes imatinib pharmacokinetics. Actual bodyweight shows slight effect on the estimated apparent clearance (CL/F) of imatinib in this study population. The final PPK model is: Ka (1/h) = 0.329; CL/F (l/h) = 9.25 × (actual bodyweight/70)0.228 ; V/F(l) = 222.
CONCLUSION: Actual bodyweight has a slight effect on CL/F. Demographics, physiopathology and pharmacogenetics covariates have no significant effects on imatinib pharmacokinetics.
METHODS: A total of 229 plasma concentrations from 170 patients were analyzed. Nonlinear mixed effect model was used to establish the PPK model.
RESULTS: A one-compartment model with first-order absorption and first-order elimination adequately describes imatinib pharmacokinetics. Actual bodyweight shows slight effect on the estimated apparent clearance (CL/F) of imatinib in this study population. The final PPK model is: Ka (1/h) = 0.329; CL/F (l/h) = 9.25 × (actual bodyweight/70)0.228 ; V/F(l) = 222.
CONCLUSION: Actual bodyweight has a slight effect on CL/F. Demographics, physiopathology and pharmacogenetics covariates have no significant effects on imatinib pharmacokinetics.
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