• Title/Summary/Keyword: Pharmacokinetic Model

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Effects of Pefloxacin Grinding on Pharmacokinetic Parameter in Korean Rockfish (조피볼락에서 Pefloxacin의 미분쇄가 약물동력학 Parameters에 미치는 영향)

  • 임영근;양영환;김진우;손상규;심경희;김유정;정한영;최우식;야마모토케이지
    • Journal of Life Science
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    • v.9 no.3
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    • pp.241-247
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    • 1999
  • Antibiotics have been routinely used to control the disease of farm-raised animals in the aquaculture facilities without any criterion based on a pharmacokinetic study. This lack of information on the effective usage of antibiotics would have brought the farmers to use excessive and/or less dosages, causing the advent of drug-resistant bacteria as well as economic loss and possible contamination of the local farming area. Until recently, few studies on a detailed manual for the antibiotic usage including chemotherapy procedure, dosage, and treatment schedule of the aquatic antibiotics have been conducted throughout the world. To the worse, there is no available criterion for optimal usage of aquatic antibiotics to control diseases in aquatic farms in this country because every country has its own aquacultural system. Therefore, based on the previous studies on the usage of the various antibiotics, our studies are to focus on the development of optimal method for the detection of various antibiotics on the fate of antibiotics applied to the fish, including absorption, circulation, and secretion physiology. Pharmacokinetic study were to sep up the optimal detective condition against residual antibiotics of fish by HPLC. The grinding pefloxacin for 15 min is most effective in dissolution test and pharmacokinetic parameters. Pharmacokinetic parameters were satisfactory for 15 min-grinding products and they can be explained as one-compartment model.

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Assay Error for Improved Pharmacokinetic Modeling and Simulation of Vancomycin (반코마이신의 약물동태학적 모델링과 시뮬레이션의 향상을 위한 분석오차)

  • Burm, Jin Pil
    • YAKHAK HOEJI
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    • v.57 no.1
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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.

Pharmacokinetic and Pharmacodynamic Modeling of Levodopa in Parkinson Disease

  • Holford, Nick H.
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.220-222
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    • 2002
  • The concentration effect relationship (pharmacokinetic pharmacodynamic model, PKPD) of drugs used for Parkinson's disease is complex. The benefits and adverse effects of drug treatment have to be considered in terms of short term and long term effects. Acute effects, observed over hours and days, reflect symptomatic benefit while chronic effects, observed over months and years, also reveal influences on the progress of the disease. (omitted)

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Mechanistic Pharmacokinetic/pharmacodynamic Modeling in Isolated Perfused Organs and at the Whole-Body Level

  • Weiss, Michael
    • Proceedings of the PSK Conference
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    • 2002.10a
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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)

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Pharmacokinetic and Pharmacological Evaluation of Topical Microemulsion Preparation Containing Piroxicam (마이크로에멀젼으로 제제 설계된 피록시캄 외용제의 약물동력학적 특성 및 약효 평가)

  • 윤범진;박은석;지상철
    • Biomolecules & Therapeutics
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    • v.7 no.1
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    • pp.54-58
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    • 1999
  • The pharmacological activities and pharmacokinetic aspects of a topical microemulsion (KDPM) containing 0.5% piroxicam were evaluated after its topical application compared with a commercially available 0.5% piroxicam gel (R gel). When the pharmacological activities were evaluated with the carrageenan-induced paw edema model, KDPM showed 55.6% edema inhibition, while R gel resulted in 37.1%. With the adjuvant-induced arthritis model, KDFM also resulted in the better pharmacological activities than R gel. The relative bioavailability of KDPM based on R gel was 176% in rabbits.

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Development of Target-Controlled Infusion system in Plasma Concentration. PART2: Design and Evaluation (혈중 목표 농도 자동 조절기(TCI) 개발 PART2: 시스템 구현 및 평가)

  • 안재목
    • Journal of Biomedical Engineering Research
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    • v.24 no.1
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    • pp.45-53
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    • 2003
  • Based on the 4-compartmental pharmacokinetic model developed in PART1, target-controlled infusion(TCI) pump system was designed and evaluated. The TCI system consists of digital board including microcontroller and digital signal process(DSP), analog board, motor-driven actuator, user friendly interface, power management and controller. It provides two modes according to the drugs: plasma target concentration and effect target concentration. Anaesthetist controls the depth of anaesthesia for patients by adjusting the required concentration to maintain both plasma and effect site in drug concentration. The data estimated in DSP include infusion rate, initial load dose, and rotation number of motor encoder. During TCI operation, plasma concentration. effect site concentration, awaken concentration, context-sensitive decrement time and system error information are displayed in real time. Li-ion battery guarantees above 2 hours without power line failure. For high reliability of the system, two microprocessors were used to perform independent functions for both pharmacokinetic algorithm and motor control strategy.

Compatibility Study between Physiologically Based Pharmacokinetic (PBPK) and Compartmental PK Model Using Lumping Method: Application to the Voriconazole Case (럼핑법을 이용한 생리학 기반 약물동태모델 및 구획화 약물동태모델 상호 호환 연구: 보리코나졸 적용 연구)

  • Ryu, Hyo-jeong;Kang, Won-ho;Chae, Jung-woo;Yun, Hwi-yeol
    • Korean Journal of Clinical Pharmacy
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    • v.31 no.2
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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.

Modified Pharmacokinetic/Pharmacodynamic model for electrically activated silver-titanium implant system

  • Tan, Zhuo;Orndorff, Paul E.;Shirwaiker, Rohan A.
    • Biomaterials and Biomechanics in Bioengineering
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    • v.2 no.3
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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.

Application of Physiologically Based Pharmacokinetic (PBPK) Modeling in Prediction of Pediatric Pharmacokinetics (생리학 기반 약물동태(PBPK, Physiologically Based Pharmacokinetic) 모델링을 이용한 소아 약물 동태 예측 연구)

  • Shin, Na-Young;Park, Minho;Shin, Young Geun
    • YAKHAK HOEJI
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    • v.59 no.1
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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.