• Toxicological Research
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• v.18 no.4
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• pp.311-324
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• 2002

Toxicokinetic studies are intended to provide critical evaluation of drug disposition at toxico-logical doses and help understand the relationship between blood or tissue levels and the time course of toxic events. Relatively high dose levels wed in toxicokinetics, compared to pharmacokinetics, complicates absorption, protein binding, metabolism and elimination processes. In this mini review, frequently wed toxicokinetic models such as linear compartment models, physiological models, and nonlinear kinetic mod-ec are introduced. In addition, optimization of toxicokinetic studies, their role in the drug development process, and prediction oj human toxicokinetics based on animal data by interspecies scaling are briefly discussed.

• Toxicological Research
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• v.13 no.3
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• pp.237-245
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• 1997

As the development of a pharmaceutical product is a dynamic process which involves continuousfeed-back between non-clinical and clinical studies, the integration of pharmacokinetics into toxicity testing became increasingly important in recent years. Toxicokinetic measurements in the toxicity studies is considered to be an important scientific approach in the interpretation of the toxicology findings and the promotion of rational study design development. Primarily this research project was conducted to determine the systemic exposure achieved in acute toxicity test and its relationship to dose level and the time course of the toxicity study. Acute hepatotoxicity study and its relevant toxicokinetic study in mice were performed using acetarninophen (AA) as a model compound. The correlation between acute hepatotoxicity indices and toxicokinetic parameters following intraperitoneally administration of various dosages of AA in mice was evaluated and discussed minutely in the text. Based on these studies, single-dose toxicity testing of AA including kinetic studies was evaluated in ICR mice for 7 days and interpreted in the text. Our results from the integration of toxicokinetic monitoring into single-dose toxicity study enable to elucidate the relation of the exposure achieved in toxicity study to toxicological findings and assist in the selection of appropriate dose levels for use in repeated-dose toxicity or later studies.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.170-170
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• 2003

DW -224a is a fluoroquinolone antibiotics with a broad spectrum of activity against Gram-positive and Gram-negative bacteria. In order to clarify toxicokinetic profile of DW-224a, a 4-week repeated dose oral toxicokinetic study (dose level: 0, 63, 250, 1000 mg/kg) was conducted in groups of Sprague-Dawley rats.(omitted)

• Environmental Analysis Health and Toxicology
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• v.24 no.2
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• pp.79-93
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• 2009

오염물질에 대한 생태위해성평가(ecological risk assessment)를 위해서는 노출평가(exposure assessment)와 함께 생물영향에 대한 평가(effect assessment)를 수행해야 한다. 노출평가의 경우는 지화학적 과정에 대한 이해를 바탕으로 환경농도를 예측하기 위한 화학평형모델이나 다매체환경거동모델 등 다양한 평가 및 예측모델을 활용해 왔다. 이와 달리 생물영향평가는 실험실 조건에서 제한된 독성자료를 대상으로 외부노출농도에 기반한 농도-반응관계를 통계적 방법을 통해서 추정하는 '경험적 모델(empirical model)'에 주로 의존해 왔다. 최근에 와서 생체 내 잔류량을 기반으로 농도-시간-반응관계를 기술하고 예측하는 독성동태학 및 독성역학 모델(toxicokinetic-toxicodynamic model)과 같은 독성작용에 기반한 모델(processbased model)들이 개발되어 활용되고 있다. 본 논문에서는 여러 종류의 독성동태학 및 독성역학 모델을 소개하고, 이를 통계적 추론에 기반한 전통적인 독성학 모델과 비교하였다. 서로 다른 종류의 독성동태학 및 독성역학 모델로부터 도출된 노출농도-시간 -반응관계식을 비교하고, 동일 독성기작을 보이는 오염물질 그룹 내에서 미측정 오염물질의 독성을 예측할 수 있게 해주는 구조-활성관계(Quantitative Structure-Activity Relationship, QSAR) 모델을 여러 독성동태 및 독성역학모델로부터 유도하였다. 마지막으로 독성동태학 및 독성역학 파라미터를 추정하기 위한 실험계획을 제안하였고, 앞으로 독성동태학 및 독성역학 모델을 생태계 위해성평가에 활용하기 위해서 해결해야 될 연구과제를 검토하였다.

• Proceedings of the Zoological Society Korea Conference
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• 1995.10b
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• pp.209.2-209
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• 1995

No Abstract, See Full Text

• Journal of Ginseng Research
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• v.35 no.3
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• pp.339-343
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• 2011

Polycyclic aromatic hydrocarbons (PAHs) are well known environmental carcinogens. PAH metabolites, especially BaP-7,8- dihydrodiol, 9,10 epoxide, initiate carcinogenesis via high specificity binding to DNA to form DNA adducts. The Korean red ginseng (KRG) from Panax ginseng has been suggested to protect against damages due to PAH exposure but the mechanism is unknown. Therefore, we investigated effects of KRG on PAH exposure using toxicokinetic methods and changes of PAH-induced oxidative damage during a 2 week-clinical trial (n=21 healthy young female, $23.71{\pm}2.43$ years). To analyze antioxidative effects of KRG, we measured changes in the levels of urinary malondialdehyde (MDA) before and after KRG treatment. We observed a significant positive association between levels of urinary MDA and 1-hydroxypyrene, a biomarker of PAH exposures (slope=1.47, p=0.03) and confirmed oxidative stress induced by PAH exposures. A reverse significant correlation between KRG treatment and level of urinary MDA was observed (p=0.03). In summary, results of our clinical trial study suggest that KRG plays a significant role in antioxidative as well as toxicokinetic pathways against PAHs exposure.

• YAKHAK HOEJI
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• v.56 no.2
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• pp.74-79
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• 2012

Citrate-capped silver nanoparticles (AgNPs) are widely used in industry, consumer products and medical appliances. However, information on the toxicity, environmental fate and toxicokinetics are not enough. In this study, stability of citrate-capped AgNPs was investigated using different types of isotonic solution, which is important in the toxicokinetic study by the exposure route of intravenous injection. Size, morphology, zeta potential and ion formation were investigated in isotonic solutions for the physico-chemical characterization of AgNPs. Aggregation and precipitation of AgNPs were observed in saline or phosphate-buffered saline while they were stable without precipitation in 2% glycerol of isotonic solution. The average size of AgNPs in 2% glycerol was 6~10 nm, which was almost same as that in water-based suspension of AgNPs. Zeta potential was ranged from -30 mV to -60 mV, which was in the range of original stock AgNPs. The stability was maintained during the whole experimental period of 48 hours. Furthermore, the stability was not changed in different temperature (10~36$^{\circ}C$) and at different concentrations (10~1,000 ppm). The osmolarity of the AgNPs suspension was $299{\pm}1$ mOsm/kg which was in isotonic range. These data suggest that AgNPs in 2% glycerol solution can be used for the preparations of intravenous injection for toxicokinetic study without undesired disturbance of blood isotonicity.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.170-170
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• 2003

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.13.1-13.4
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• 2016

An analysis of patients and fatalities due to exposure to polyhexamethylene guanidine (PHMG) shows that PHMG causes mainly lung diseases such as pulmonary fibrosis. However, no research on the other organs has been conducted on this matter yet. So, an in-depth discussion on toxicological techniques is needed to determine whether or not PHMG is toxic to organs other than just the lungs. For the test of target organ toxicity by PHMG exposure, a toxicokinetic study must first be conducted. However, measurement method for PHMG injected into the body has not yet been established because it is not easy to analyze polymer PHMG, so related base studies on analytical technique for PHMG including radio-labeling chemistry must come first. Moreover, research on exposure-biomarker and effect-biomarker must also be conducted, primarily related to clinical application. Several limitations seem to be expected to apply the biomarker study to the patient because much time has passed after exposure to the humidifier disinfectant. It is why a more comprehensive toxicological researches must be introduced to the causality for the victims.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.163-163
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• 2002