Population pharmacokinetics of imatinib mesylate in healthy Korean subjects

Park, Gab-jin; Park, Wan-Su; Bae, Soohyun; Park, Sung Min; Han, Seunghoon

doi:10.12793/tcp.2016.24.2.96

Cited by 7 publications

(14 citation statements)

References 22 publications

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“…In general, model performance bias improved (median of IPE closer to zero) as additional information was taken into account together with the increase in the variability of this metric. The popPK models evaluated provided adequately unbiased individual predictions (IPE close to zero) considering the first two imatinib TDM visits or samples, except the one developed by Park et al 52 Models with relatively biased predictions for the first occasion experienced the greatest benefits in precision and bias improvement by the addition of individual PK information. Overall, dispersion of IPE was significantly lower in those models including IOV when additional individual PK information is considered.…”

Section: Resultsmentioning

confidence: 87%

“…The bias of the imatinib popPK models evaluated is shown in Figure 1. Most of the models showed a slightly acceptable negative bias except the model proposed by Park et al, 52 which showed pronounced biased results (systematic underprediction). The smaller bias was presented for the models proposed by Eechoute et al, 58 Debaldo et al 55 and Wang et al, 53 with a MPE close to zero.…”

Section: Resultsmentioning

confidence: 93%

“…Several valuable popPK models were not selected for this analysis for the following reasons: incomplete structural model, covariate relationship or stochastic model reported, 11,44–46 joint model of free and total imatinib plasma concentrations 11,47 . Candidate models were developed mainly in CML patients (n = 8) 18,48–54 or subjects diagnosed with gastrointestinal stromal tumours (GIST) (n = 4) 55–58 . The popPK models selected were developed in Caucasian (n = 11) or Asian populations (n = 3) 49,52,53 and mainly fitted to a one‐compartment PK model (n = 12).…”

Section: Resultsmentioning

confidence: 99%

“…Summary of population pharmacokinetic models of imatinib evaluated All pharmacokinetic models describe a first order linear elimination. All pharmacokinetic models were developed in Caucasian population with the exception of three models which were developed in Asian population 49,52,53. The imatinib administration route was orally on all models except in Demetri model was intramuscular.…”

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confidence: 99%

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External evaluation of population pharmacokinetic models of imatinib in adults diagnosed with chronic myeloid leukaemia

Alaejos

Castañeda

Cabrera

et al. 2021

Brit J Clinical Pharma

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Imatinib is considered the standard first-line treatment in newly diagnosed patients with chronic-phase myeloid leukaemia (CML). Several imatinib population pharmacokinetic (popPK) models have been developed. However, their predictive performance has not been well established when extrapolated to different populations. Therefore, this study aimed to perform an external evaluation of available imatinib popPK models developed mainly in adult patients, and to evaluate the improvement in individual model-based predictions through Bayesian forecasting computed by each model at different treatment occasions. Methods: A literature review was conducted through PubMed and Scopus to identify popPK models. Therapeutic drug monitoring data collected in adult CML patients treated with imatinib was used for external evaluation, including prediction-and simulated-based diagnostics together with Bayesian forecasting analysis. Results: Fourteen imatinib popPK studies were included for model-performance evaluation. A total of 99 imatinib samples were collected from 48 adult CML patients undergoing imatinib treatment with a minimum of one plasma concentration measured at steady-state between January 2016 and December 2020. The model proposed by Petain et al showed the best performance concerning prediction-based diagnostics in the studied population. Bayesian forecasting demonstrated a significant improvement in predictive performance at the second visit. Inter-occasion variability contributed to reducing bias and improving individual model-based predictions. Conclusions: Imatinib popPK studies developed in Caucasian subjects including α1-acid glycoprotein showed the best model performance in terms of overall bias and precision. Moreover, two imatinib samples from different visits appear sufficient to reach an adequate model-based individual prediction performance trough Bayesian forecasting.

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Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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External evaluation of population pharmacokinetic models of imatinib in adults diagnosed with chronic myeloid leukaemia

Alaejos

Castañeda

Cabrera

et al. 2021

Brit J Clinical Pharma

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“…Although it is more a descriptive model than a mechanistic model, in vivo drug absorption is a complex multistage process, and the flexibility inherent in the Weibull function may reflect the actual variable drug absorption rates changing along the gastrointestinal tract [33]. This model is often used as an alternative to describe the complicated absorption profile when simple-order kinetics cannot describe it adequately [34,35,36,37,38,39]. The first-order and zero-order framework failed to depict the absorption phases of CKD519 in the three species tested here, but these were well described by the Weibull-type absorption model, which showed that it was plausible to infer this model as a human absorption model.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Prediction of Human Pharmacokinetics and Pharmacodynamics of CKD519, a Potent Inhibitor of Cholesteryl Ester Transfer Protein (CETP)

Choi

Han

Jeon³

2019

Pharmaceutics

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CKD519, a selective inhibitor of cholesteryl ester transfer protein(CETP), is undergoing development as an oral agent for the treatment of primary hypercholesterolemia and mixed hyperlipidemia. The aim of this study was to predict the appropriate efficacious dose of CKD519 for humans in terms of the inhibition of CETP activity by developing a CKD519 pharmacokinetic/pharmacodynamic (PK/PD) model based on data from preclinical studies. CKD519 was intravenously and orally administered to hamsters, rats, and monkeys for PK assessment. Animal PK models of all dose levels in each species were developed using mixed effect modeling analysis for exploration, and an interspecies model where allometric scaling was applied was developed based on the integrated animal PK data to predict the human PK profile. PD parameters and profile were predicted using in vitro potency and same-in-class drug information. The two-compartment first-order elimination model with Weibull-type absorption and bioavailability following the sigmoid Emax model was selected as the final PK model. The PK/PD model was developed by linking the interspecies PK model with the Emax model of the same-in-class drug. The predicted PK/PD profile and parameters were used to simulate the human PK/PD profiles for different dose levels, and based on the simulation result, the appropriate efficacious dose was estimated as 25 mg in a 60 kg human. However, there were some discrepancies between the predicted and observed human PK/PD profiles compared to the phase I clinical data. The huge difference between the observed and predicted bioavailability suggests that there is a hurdle in predicting the absorption parameter only from animal PK data.

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Role of ADME gene polymorphisms on imatinib disposition: results from a population pharmacokinetic study in chronic myeloid leukaemia

Shriyan

Mehta

Patil

et al. 2022

Eur J Clin Pharmacol

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Population pharmacokinetics of imatinib mesylate in healthy Korean subjects

Cited by 7 publications

References 22 publications

External evaluation of population pharmacokinetic models of imatinib in adults diagnosed with chronic myeloid leukaemia

External evaluation of population pharmacokinetic models of imatinib in adults diagnosed with chronic myeloid leukaemia

Quantitative Prediction of Human Pharmacokinetics and Pharmacodynamics of CKD519, a Potent Inhibitor of Cholesteryl Ester Transfer Protein (CETP)

Role of ADME gene polymorphisms on imatinib disposition: results from a population pharmacokinetic study in chronic myeloid leukaemia

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