• 약학회지
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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.

• 한국임상약학회지
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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.

• 한국독성학회:학술대회논문집
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• 한국독성학회 1998년도 국제심포지움 및 추계학술대회
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• pp.50-50
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• 1998

• 한국임상약학회지
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• 제18권2호
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• pp.84-96
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• 2008

In the recent, pharmacokinetic (PK)/pharmacodynamic (PD) modeling has appeared as a critical path tools in new drug development to optimize drug efficacy and safety. PK/PD modeling is the mathematical approaches of the relationships between PK and PD. This approach in new drug development can be estimated inaccessible PK and PD parameters, evaluated competing hypothesis, and predicted the response under new conditions. Additionally, PK/PD modeling provides the information about systemic conditions for understanding the pharmacology and biology. These advantages of PK/PD model development are to provide the early decision-making information in new drug development process, and to improve the prediction power for the success of clinical trials. The purpose of this review article is to summarize the PK/PD modeling process, and to provide the theoretical and practical information about widely used PK/PD models. This review also provides model schemes and the differential equations for the development of PK/PD model.

• 약학회지
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• 제45권2호
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• pp.153-160
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• 2001

This research developed an intravenous (IV) vancomycin dosing nomogram based on the clinical pharmacokinetic data of Korean adult patients. Total 99 pairs of steady-state peak and trough serum concentrations of vancomycin were obtained from 73 adult patients in a tertiary general hospital. Serum vancomycin concentrations were determined to assess the appropriateness of initial vancomycin dosing. Only 47.2% of the cases were within therapeutic range. To characterize the clinical pharmacokinetics (PK) of vancomycin, PK parameters including elimination rate constant ( $K_{e}$) half-life( $T_{1}$2/), clearance (C $l_{van}$), volume of distribution ( $V_{d}$) were calculated by using one-compartment, first order pharmacokinetic equations. PK parameters were evaluated based on the differences of patients'renal function and age. Regression analysis showed a significant correlation between C $l_{van}$ and $C_{cr}$ (C $l_{van}$ = -1.89+0.914 $C_{cr}$ , r=0.763) and between $K_{e}$ and $C_{cr}$ , ( $K_{e}$=-0.0037+0.00139 $C_{cr}$ =0.724). The relationship between $K_{e}$ and $C_{cr}$ , and the mean $V_{d}$ were utilized for developing the nomogram to individualize the initial dosing regimen of vancomycin for the patients with various degrees of renal functions. The nomogram may be used as an efficient tool to determine safe and effective doses of vancomycin for the Korean adult patients.nts.nts.nts.s.nts.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.88-89
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• 2003

In recent days, the bioequivalence(BE) study of domestic drugs on original drug are quite, activated in Korea. This BE study provide not only the bioequivalence of test and reference drug but also produce the population pharmacokinetic(PK) parameters in normal healthy Korean. The BE study can also make it possible to establish a PK/PD model of the drug when the additional pharmacodynamic(PD) data are available. (omitted)

• 대한예방의학회:학술대회논문집
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• 대한예방의학회 1996년도 제48차 추계 학술대회 연제집
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• pp.179-180
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• 1996

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.143-143
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• 2002

• Biomaterials and Biomechanics in Bioengineering
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• 제2권3호
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• pp.127-141
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• 2015

Silver-based systems activated by low intensity direct current continue to be investigated as an alternative antimicrobial for infection prophylaxis and treatment. However there has been limited research on the quantitative characterization of the antimicrobial efficacy of such systems. The objective of this study was to develop a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model providing the quantitative relationship between the critical system parameters and the degree of antimicrobial efficacy. First, time-kill curves were experimentally established for a strain of Staphylococcus aureus in a nutrientrich fluid environment over 48 hours. Based on these curves, a modified PK/PD model was developed with two components: a growing silver-susceptible bacterial population and a depreciating bactericidal process. The test of goodness-of-fit showed that the model was robust and had good predictability ($R^2>0.7$). The model demonstrated that the current intensity was positively correlated to the initial killing rate and the bactericidal fatigue rate of the system while the anode surface area was negatively correlated to the fatigue rate. The model also allowed the determination of the effective range of these two parameters within which the system has significant antimicrobial efficacy. In conclusion, the modified PK/PD model successfully described bacterial growth and killing kinetics when the bacteria were exposed to the electrically activated silver-titanium implant system. This modeling approach as well as the model itself can also potentially contribute to the development of optimal design strategies for other similar antimicrobial systems.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.223-224
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• 2002

Pharmacokinetic (PK) and pharmacodynamic (PD) study of a new reversible proton pump inhibitor (YH1885, Yuhan Pharmaceutical Co.) was done as a phase 1 clinical trial in Seoul national University Hospital Clinical trialcenter. Single dose of 60, 100, 150, 200, and 300mg were administered to total 20 healthy subjects under fasting state. Six subjects were given 100 mg after food and 12 subjects were given multiple doses of 150 and 300 mg every day for 7 days under fasting state. (omitted)