• Proceedings of the PSK Conference
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.84-87
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• 2003

The purposes of this study were to evaluate the population pharmacokinetics of levosulpiride and terbinafine according to several pharmacokinetic models and to investigate the influence of characteristics of subjects such as age, body weight, height and serum creatinine concentration on the pharmacokinetic parameters of levosulpiride and terbinafine, respectively. (omitted)

• The Korean Journal of Applied Statistics
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• 제34권1호
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• pp.9-23
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• 2021

In the following paper we introduce a variational Bayes method that approximates posterior distributions with mean-field method. In particular, we introduce automatic differentiation variation inference (ADVI), which approximates joint posterior distributions using the product of Gaussian distributions after transforming parameters into real coordinate space, and then apply it to pharmacokinetic models that are models for the study of the time course of drug absorption, distribution, metabolism and excretion. We analyze real data sets using ADVI and compare the results with those based on Markov chain Monte Carlo. We implement the algorithms using Stan.

• YAKHAK HOEJI
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• 제57권1호
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• pp.32-36
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• 2013

The purpose of this study was to determine the influence of assay error for improved pharmacokinetic modeling and simulation of vancomycin on the Bayesian and nonlinear least squares regression analysis in 24 Korean gastric cancer patients. Vancomycin 1.0 g was administered intravenously over 1 hr every 12 hr. Three specimens were collected at 72 hr after the first dose from all patients at the following times, at 0.5 hr before regularly scheduled infusion, at 0.5 hr and 2 hr after the end of 1 hr infusion. Serum vancomycin levels were analyzed by fluorescence polarization immunoassay technique with TDX-FLX. The standard deviation (SD) of the assay over its working range had been determined at the serum vancomycin concentrations of 0, 20, 40, 60, 80 and $120{\mu}g/ml$ in quadruplicate. The polynomial equation of vancomycin assay error was found to be SD $({\mu}g/ml)=0.0224+0.0540C+0.00173C^2$ ($R^2=0.935$). There were differences in the influence of weight with vancomycin assay error on pharmacokinetic parameters of vancomycin using the nonlinear least squares regression analysis but there were no differences on the Bayesian analysis. This polynomial equation can be used to improve the precision of fitting of pharmacokinetic models to optimize the process of model simulation both for population and for individualized pharmacokinetic models. The result suggests the improvement of dosage regimens for the better and safer care of patients receiving vancomycin.

• Proceedings of the PSK Conference
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.218-219
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• 2002

In the past, the development of pharmacokinetic/pharmacodynamic (PK/PD) models for quantitating the time course of drug responses was mainly based on two types of models, the empirical effect compartment model that simply accounts for the delay between effect and plasma concentration (hysteresis) and the mechanism-based so-called indirect response model. The first approach traces back to a paper by Segre (1) and its application was popularized by Holford and Sheiner (2); indirect response models were introduced by Jusko's group (3). (omitted)

• YAKHAK HOEJI
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• 제59권1호
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• pp.29-39
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• 2015

In recent years, physiologically based pharmacokinetic (PBPK) modeling has been widely used in pharmaceutical industries as well as regulatory health authorities for drug discovery and development. Several application areas of PBPK have been introduced so far including drug-drug interaction prediction, transporter-mediated interaction prediction, and pediatric PK prediction. The purpose of this review is to introduce PBPK and illustrates one of its application areas, particularly pediatric PK prediction by utilizing existing adult PK data and in vitro data. The evaluation of the initial PBPK for adult was done by comparing with experimental PK profiles and the scaling from adult to pediatric was conducted using age-related changes in size such as tissue compartments, and protein binding etc. Sotalol and lorazepam were selected in this review as model drugs for this purpose and were re-evaluated using the PBPK models by GastroPlus$^{(R)}$. The challenges and strategies of PBPK models using adult PK data as well as appropriate in vitro assay data for extrapolating pediatric PK at various ages were also discussed in this paper.

• Archives of Pharmacal Research
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• 제10권4호
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• pp.250-257
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• 1987

The development of physiologically based pharmacokinetic model for drug distribution and excretion is described. The physiological modeling procedure is useful in animal and clinical applications to obtain fundamental knowledge of the transport and metabolism of a substance in vivo. In this paper a review of physiologically based pharmacokinetics is presented in the hope of understanding and increasing the use of this modelling technique. The method of model development and the composition of equations based on the different models are explained. For the better understanding a physiological pharmacokinetic model of tenoxicam disposition in the rat is presented as an example of flow limited model.

• Proceedings of the Korean Society of Applied Pharmacology
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• 한국응용약물학회 1995년도 제3회 추계심포지움
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• pp.135-136
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• 1995

Resent advances in computer technology have introduced a sophisticated capability for computing the biological fate of toxicants in a biological system. This methodology, which has drastically altered risk assessment skill in toxicology, is designed using all the mechanistic information, and all claim better accuracy with extrapolating capability Iron animal to people than conventional pharmacokinetic methods. Biologically based mathematical models in which the specific mechanistic steps governing tissue disposition(pharmacokinetics) and toxic action (pharmacodynamics) of chemicals are constructed in quantitative terms by a set of equations loading to prediction of the outcome of specific toxicological experiments by computer simulation. pharmacokinetic and pharmacodynamic models are useful in risk assessment because their mechanistic biological basis permits the high-to-low dose, route to route and interspecies extrapolation of the tissue disposition and toxic action of chemicals.

• The Korean Journal of Applied Statistics
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• 제25권1호
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• pp.139-152
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• 2012

The result of the analysis of a population pharmacokinetic model can directly influence the decision of the dose level applied to the targeted patients. Therefore the validation procedure of the final model is very important in this area. This paper reviews the validation methods of population pharmacokinetic models from a statistical viewpoint. In addition, the whole procedure of the analysis of population pharmacokinetics, from the base model to the final model (that includes various validation procedures for the final model) is tested with real clinical data.

• Korean Journal of Clinical Pharmacy
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• 제31권2호
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• pp.125-135
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• 2021

Background: Generally, pharmacokinetics (PK) models could be stratified into two models. The compartment PK model uses the concept of simple compartmentalization to describe complex bodies, and the physiologically based pharmacokinetic (PBPK) model describes the body using multi-compartment networking. Notwithstanding sharing a theoretical background in both models, there was still a lack of knowledge to enhance compatibility in both models. Objective: This study aimed to evaluate the compatibility among PBPK, lumping model and compartment PK model with voriconazole PK case study. Methods: The number of compartments and blood flow on each tissue in the PBPK model were modified using the lumping method, considering physiological similarities. The concentration-time profiles and area under the concentration-time curve (AUC) parameters were simulated at each model, assuming taken voriconazole oral 400 mg single dose. After that, those mentioned PK parameters were compared. Results: The PK profiles and parameters of voriconazole in the three models were similar that proves their compatibility. The AUC of central compartment in the PBPK and lumping model was within a 2-fold range compared to those in the 2- compartment model. The AUC of non-eliminating tissues compartment in the PBPK model was similar to those in the lumping model. Conclusion: Regarding the compatibility of the three PK models, the utilization of the lumping method was confirmed by suggesting its reliable PK parameters with PBPK and compartment PK models. Further case studies are recommended to confirm our findings.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2006년도 제15차 추계학술대회
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• pp.37-38
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• 2006