• 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.

• Journal of Applied Biological Chemistry
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• v.57 no.3
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• pp.235-242
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• 2014

The purpose of this study is the establishment of scientific processes for making food safety policies. Thus, we investigated pesticide residue level of the agricultural commodities from market, and performed risk assessment. Fifteen agricultural items are chosen based on the frequency of Korean consumption. The samples were collected from 9 cities where populations are more than one million. Total 283 active ingredients were monitoring ( total sample number =232). Single-analysis of target pesticides was for three kinds of possible growth regulators and the multicomponent analysis was for 280 kinds of pesticides, a total of 283 species were selected to perform the pesticide residues. Before monitoring the analytes, the improvements of the analytical methods were done by method validations under the CODEX analytical method development guidelines and can produce metrics that represent the international standards applied in accordance with the guidelines. In addition to residual pesticides detected during monitoring we compare the ADI to EDI values using detected result and dietary consumption data which is extracted from annual market basket survey. The 163 samples were non-detected in the total 232 samples so it means that every agricultural commodity will residual pesticides-free in 70.3%. The detected residual pesticides showed for a total of 69 cases (29.7%). Two of samples violate Korean MRL (0.9%). The ratio of EDI compared to ADI resulted in only from 0.00087 to 0.902%. In result, we can assume that all detected residual pesticides are very safe level and current policies of Korean pesticides control may be working.

• Herbal Formula Science
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• v.25 no.3
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• pp.391-412
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• 2017

Objective : In this study, we searched the experimental research about combined treatment of anticancer drug and herbal medicine for killing or inhibiting proliferation of Cancer cells searched in OASIS and KISS. This study aimed to analyze the experimental research paper about anticancer drug combined treatment with herbal medicine. Methods : We collected the research paper including killing or inhibiting proliferation of Cancer cells in OASIS and KISS using keyword anticancer drug with herbal medicine, tumor suppressor with herbal medicine, inhibition of Cancer with herbal medicine and combined treatment with herbal medicine. Assorting by cancer cells, we analyzed experimental results cancer cell viability, anticancer drug dosage, tumor weight and survival rate. Also, we checked the effects of herbal medicine on cancer and additive effect reducing side effect of anticancer drug. Results : Total 45 studies were selected. 38 studies reported combined treatment of anticancer drug and herbal medicine was more effective than only anticancer drug. The death of cancer cells was synergistically induced by the cotreatment of anticancer drug and herb extracts. The studies suggest that the cotreatment of anticancer drug and herb extracts could reduce side effect of anticancer drug. In addition, some studies reported cotreatment mechanism like apoptotic death signal processes. In combined treatment of anticancer drug and herb extracts, The expression of Fas/Fas L, Bax, Bcl2, Caspase-3 etc.. was markedly increased in cancer cells. Conclusions : Our results suggest that anticancer drug combined treatment with herbal medicine could be efficient for killing or inhibiting proliferation of cancer cells. However, this paper had some limitation as follows: First, collected studies have been published only for korean journal. Second, results of research and effects of combined treatment are not collected objectively. To solve these problems, more objective and balanced studies should be performed.

• Korean Journal of Community Nutrition
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• v.3 no.1
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• pp.76-93
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• 1998

Three hundred sixty-two(male 131, female 231) elderly aged over 65 in Chungb- uk area were interviewed to determine the disease states and drug usage patterns. The prebalence of disease was 78% and women reported more chronic diseases(83%) than men(71%). Elderly who live with spouse and have an occupation have a lower rate of disease. Average number of diseases of the elderly was $1.8\pm{1.1}$, and women$(2.1\pm{1.3)}$ have significantly higher average number of diseases than that of men$(1.4\pm{0.7)}$. Also the elderly in urban areas$(2.1\pm{1.4)}$ have significantly higher number of diseases than that of the elderly in rural areas$(1.6\pm{0.9)}$. Arthritis, hypertension, cardiovascular and gastric diseases were the most frequently listed chronic diseases in order for both men and women. Anemia and fracture of bone were relatively higher in women than in men. Particularly, the arthritis of the urban elderly have a rate of 1.5 times higher than that of the rural elderly. Fifty-two percent of the elderly were currently using drugs ; among drug users 71.2% used prescription drugs and 20.5% used nonprescription drugs. The average number taken per person was 2.1$\pm$1.4 and there was no sex or age difference. However, the elderly in rural areas $(2.7\pm{1.7)}$ consumed a significantly higher number of drugs than those in urban areas$(1.7\pm{0.7)}$. The average number of prescripti- on drugs taken was 2.0$\pm$1.4 while the average of nonprescription drugs taken was $(1.3\pm{0.6)}$. Analgesics and antihypertensive drugs were most commonly used. Vitamin and analgesics were the most frequently used self-prescribed drugs. It was noted that potential adverse drug interaction by concominant drug consumption for arthritis and antihypensive drug, abuse of digestants and antiacid without treatment of the underlying disease, and misuse of quick-acting bowel medications were problematic for the elderly. In addition drugs used for the elderly have some adverse effect on the digestive system. The types and composition of drugs used by the elderly were identified and presented. Medication compliance was poor and 13.5% reported adverse reactions such as edema, heartburn, nausea, and difficulty with eating. Seventeen percent of the elderly obtained drugs arranged by those other than medical staff. Also, even among those elderly who obtained drugs prescribed by a doctor, 69.1% of subjects had not receive instruction about potential adverse reactions. These results suggest that nutritional problems related to drug usage might exist and so dietitians, either individually or as members of health teams, need to have a better understanding of drug-nutrient interaction and closer supervision, and drug information/education service should therefore be provided to prevent or minimize adverse drug reaction in elderly users of medication.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.718-723
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• 2002

CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) is a recently-developed synthetic camptothecin analogue and currently under clinical development by Chong Kun Dang Pharm (Seoul, Korea). CKD-602 showed potent topoisomerase inhibitory activity in vitro and broad antitumor activity against various human tumor cells in vitro and in vivo in animal models. This study describes the pharmacodynamics of the immediate and delayed cytotoxicity induced by CKD-602 in a human colorectal adenocarcinoma cell line, HT-29, and its intracellular drug accumulation by HPLC. The present study was designed to address whether the higher activity of CKD-602 with prolonged exposure is due to delayed exhibition of cytotoxicity and/or an accumulation of anti proliferative effect on continuous drug exposure. The drug uptake study was performed to determine whether the delayed cytotoxicity is due to a slow drug accumulation in cells. CKD-602 produced a cytotoxicity that was exhibited immediately after treatment (immediate effect) and after treatment had been terminated (delayed effect). Both the immediate and delayed effects of CKD-602 showed a time dependent decrease in 4IC_{50}$ values. Drug uptake was biphasic and the second equilibrium level was obtained as early as at 24hr, indicating that the cumulative and delayed antitumor effects of CKD-602 were not due to slow drug uptake. On the other hand, CKD-602 treatment was sufficient to induce delayed cytotoxicity after 4hr, however, longer treatment (＞24hr) enhanced its cytotoxicity due to the intracellular accumulation of the drug, which requires 24hr to reach maximum equilibrium concentration. In addition, $C^n$$\times$T=h analysis (n=0.481) indicated that increased exposure times may contribute more to the overall antitumor activity of CKD-602 than drug concentration. Additional studies to determine the details of the intracellular uptake kinetics (e.g., concentration dependency and retention studies) are needed in order to identify the optimal treatment schedules for the successful clinical development of CKD-602.

• Korean Journal of Environmental Agriculture
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• v.41 no.2
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• pp.135-151
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• 2022

BACKGROUND: The β-agonists known as phenyl ethanolamine derivatives have a conjugated aromatic ring with amino group. They are used as tocolytic agents and bronchodilator to human and animal generally, and some of them are used as growth promoters to livestock. METHODS AND RESULTS: β-agonists in samples were extracted by 0.4 N perchloric acid and ethyl acetate. The target compounds were analyzed by liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS). Validation of method was performed according to CODEX guidelines (CAC/GL-71). The matrix matched calibration gave correlation coefficients>0.98, and the obtained recoveries were in the range of 62.0-109.8%, with relative standard deviation ≤ 20.1%. In addition, a survey was performed to inspect any residual β-agonist from 100 samples of livestock and fishery products and ractopamine was detected in one of the 100 samples. CONCLUSION(S): In this study, we established the analytical method for β-agonists through using the expanded target compounds and samples. And we anticipate that the established method would be used for analysis to determine veterinary drug residues in livestock and fishery products.

• Archives of Pharmacal Research
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• v.22 no.3
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• pp.262-266
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• 1999

Dopamine transporter (DAT) plays the most important role in terminating the actions of dopamines released into the synaptic cleft. DAT is also the target of various psychotropic drugs such as cocaine and amphetamine. In this study were prepared DAT-specific antibodies using the 2nd extracellular loop of rat DAT as an antigen. The 2nd extracellular loop of the rat DAT was expressed in bacterial as a fusion protein with glutathione-S-transferase, and injected ito rabbits to raise antibodies. Produced antibodies clearly recognized the rat DAT in ELISA, immunoblotting, and immumoprecipitation. As expected from the high sequence homology between the rat and human DAT, the antibodies raised for the rat DAT cross-reacted with the human DAT in the immunoblotting. Considering the specificity for DAT with wide range of applications such as ELISA, immunoblotting, and immunoprecipitation, these antibodies would be valuable tool for understanding the pharmacological actions of dopamine transporter and drug addition.

• Journal of Dental Anesthesia and Pain Medicine
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• v.21 no.4
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• pp.369-376
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• 2021

In adult patients with dental phobia, dental treatment may be difficult, or may not be possible. Depending on the level of fear or anxiety, non-pharmacological or pharmacological behavior management techniques are used in the dental treatment of such patients. Among the pharmacological behavior management techniques, minimal sedation, that is, the lowest depth of sedation, can be easily obtained in adult patients using oral sedatives, does not require special equipment or tools, and does not affect ventilatory and cardiovascular function. Diazepam is an anxiolytic drug belonging to the benzodiazepine family that, in addition to relieving anxiety, produces muscle relaxation, and is a representative drug used in adult patients with fear of dental treatment. Herein, we report the case of a 50-year-old woman with severe dental fear who successfully underwent long-term dental treatment in approximately 20 visits with minimal sedation using oral diazepam. In addition, we reviewed the considerations for the use of benzodiazepines for minimal sedation.

• The Korean Society of Law and Medicine
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• v.13 no.2
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• pp.79-113
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• 2012

This study focuses on the protection of trial subjects, who participate in clinical trials for new drug. It takes long time to develop new drugs and the clinical trials are required. Usually, pharmaceutical company, which develop new drug, request a research institution(usually, hospital) to investigate the examination of security and side effects of new drug. The institution recruit trial subject to participate in the trials. The contract for clinical research of investigational new drug is concluded between the pharmaceutical company and the institution. This thesis studies the legal regulations for protection of participants of clinical research for new drug. In this respect the first matter of this study is to seek which relation between pharmaceutical firm and participants of clinical trials. Especially, there is a question which the trial subject is entitled to demand the pharmaceutical company which requested clinical trials the institution to supply the investigational new drug, after the contract for clinical trials had terminated or cancelled. This study take into account the liability of the pharmaceutical company to trial subject. Secondly, it is researched the roles and authority of Institutional Review Board(IRB). IRB is Research Ethics Committee of the institution, in which clinical trials for new drug are conducted. According to the rule of Korea good clinical practice(KGCP), IRB is the mandatory organization which is authorized to approve, secure approval or disapprove the clinical trials for investigational new drug in the institution. The important roles are the review of ethical perspective of trial research and the protection of trial subject. Thirdly, this paper focuses if the participants are to be paid for the participation for clinical research. This is ethical aspect of clinical trials. It is resonable that the participant is reimbursed for expenditure such as travels, and other expenses incurred in participation in trials. It is not allowed that the benefit of clinical trials is paid to trial subject. The payment should not function as financial inducements for participations of trials. Finally, the voluntary consent of the trial subject is required. The institution ought to inform the subject, who would like to participate in trials, and it ought to received informed consent in writing for subject. In this regard, it is matter that trial subject has ability of consent. It is principle that the subject as severely psychogeriatric patient has not ability of consent. However, it is required that not only healthy people but also patients are allowed to take part in clinical trials of new drug, in order to confirm which the investigation new drug is secure. Therefore there are cases, in which the legal representative of subject consent the participation of the trials. In addition, it is very important that the regulations concerning clinical trials of new drug is to be systematically well-modified. The approach of legal and political approach is needed to achieve this purpose.

• Korean Journal of Environmental Agriculture
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• v.40 no.2
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• pp.108-117
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• 2021

BACKGROUND: Dichlobentiazox is a newly registered pesticide in Korea as a triazole fungicide and requires establishment of an official analysis method for the safety management. Therefore, the aim of this study was to determine the residual analysis method of dichlobentiazox for the five representative agricultural products. METHODS AND RESULTS: Three QuEChERS methods were applied to establish the extraction method, and the EN method was finally selected through the recovery test. In addition, various adsorbent agents were applied to establish the clean-up method. As a result, it was found that the recovery of the tested pesticide was reduced when using the d-SPE method with PSA and GCB, but C₁₈ showed an excellent recovery. Therefore this method was established as the final analysis method. For the analysis, LC-MS/MS was used with consideration of the selectivity and sensitivity of the target pesticide and was operated in MRM mode. The results of the recovery test using the established analysis method and inter laboratory validation showed a valid range of 70-120%, with standard deviation and coefficient of variation of less than 3.0% and 11.6%, respectively. CONCLUSION: Dichlobentiazox could be analyzed with a modified QuEChERS method, and the method determined would be widely available to ensure the safety of residual pesticides in Korea.