• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.107-115
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• 2017

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the "fit for purpose" application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in $C_{max}$ of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.

• Information Systems Review
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• v.24 no.1
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• pp.21-37
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• 2022

Drug repositioning, one of the methods of developing new drugs, is a useful way to discover new indications by allowing drugs that have already been approved for use in people to be used for other purposes. Recently, with the development of machine learning technology, the case of analyzing vast amounts of biological information and using it to develop new drugs is increasing. The use of machine learning technology to drug repositioning will help quickly find effective treatments. Currently, the world is having a difficult time due to a new disease caused by coronavirus (COVID-19), a severe acute respiratory syndrome. Drug repositioning that repurposes drugsthat have already been clinically approved could be an alternative to therapeutics to treat COVID-19 patients. This study intends to examine research trends in the field of drug repositioning using machine learning techniques. In Pub Med, a total of 4,821 papers were collected with the keyword 'Drug Repositioning'using the web scraping technique. After data preprocessing, frequency analysis, LDA-based topic modeling, random forest classification analysis, and prediction performance evaluation were performed on 4,419 papers. Associated words were analyzed based on the Word2vec model, and after reducing the PCA dimension, K-Means clustered to generate labels, and then the structured organization of the literature was visualized using the t-SNE algorithm. Hierarchical clustering was applied to the LDA results and visualized as a heat map. This study identified the research topics related to drug repositioning, and presented a method to derive and visualize meaningful topics from a large amount of literature using a machine learning algorithm. It is expected that it will help to be used as basic data for establishing research or development strategies in the field of drug repositioning in the future.

• YAKHAK HOEJI
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• v.51 no.6
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• pp.440-446
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• 2007

Arcabose is a competitive inhibitor of the intestinal ${\alpha}$-glucosidases and reduces the postprandial digestion and absorption of carbohydrate and disaccharides. Due to its negligible oral absorption, measuring drug concentration in the plasma is impractical. Thus, the common pharmacokinetic study is not available to determine the bioequivalence of the generic acarbose preparations. The aim of this study is the establishment of pharmacodynamic assessment method for the bioequivalence test of the generic acarbose preparations. Placebo-controlled cross-over ($3{\times}3$) clinical study was conducted in 23 healthy volunteers. Volunteers received a single oral dose of placebo, reference drug ($Glucoby^{(R)}$ 100 mg, Lot # D043) or test drug ($Glucoby^{(R)}$ 100 mg, Lot # E005) just before breakfast, then blood samples for evaluation of serum glucose and insulin levels were taken during for 4 hours. $C_{max},\;AUC_{0-2},\;AUC_{0-4},\;{\Delta}C_{max},\;{\Delta}AUC_{0-2}\;and\;{\Delta}AUC_{0-4}$ of the postprandial plasma glucose level significantly decreased when a single dose of acarbose 100 mg preparations was administered. However, any significant difference was not detected between the groups taken the reference drug and the test drug. These results proposed that the pharmacodynamic protocols of this study is suitable to use for bioequivalence test of acarbose preparations. On the basis of the results of this study and the data of literature on this subject, the standard protocols of bioequivalence study of acarbose preparation are proposed.

• Journal of Food Hygiene and Safety
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• v.32 no.5
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• pp.381-388
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• 2017

In this study, we investigated the levels of natural preservatives of benzoic acid, sorbic acid, and propionic acid in spices. The quantitative analysis was performed using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) for benzoic acid and sorbic acid and gas chromatography-mass spectrometry (GC-MS) for propionic acid. The sample was extracted with ethanol using sonication, then centrifuged and evaporated to dryness and redissolved to 1 mL with ethanol to use for the instrumental analysis. The analytical method was validated based on linearity, recovery, limit of detection (LOD), and limit of quantification (LOQ). This method was suitable to determine low amounts of naturally occurring preservatives (benzoic acid, sorbic acid, and propionic acid) in various spices. Benzoic acid, sorbic acid, and propionic acid were found in 165 samples, 88 samples, and 398 samples, respectively from the total of 493 samples. The concentration of benzoic acid, sorbic acid, and propionic acid were ranged at ND-391.99 mg/L, ND-57.70 mg/L, and ND-188.21 mg/L in spices, respectively. The highest mean levels of benzoic acid, sorbic acid, and propionic acid were found in cinnamon (167.15 mg/L), basil leaves (22.79 mg/L), and white pepper (51.48 mg/L), respectively. The results in this study provide ranges of concentration regarding naturally occurring benzoic acid, sorbic acid, and propionic acid in spices. Moreover, the results may use to the case of consumer complaint or trade friction due to the inspection services of standard criteria for the preservatives of spices.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.191-199
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• 2000

Genomics is providing targets faster than we can validate them and combinatorial chemistry is providing new chemical entities faster than we can screen them. Historically, the drug discovery cascade has been established as a sequential process initiated with a potency screening against a selected biological target. In this sequential process, pharmacokinetics was often regarded as a low-throughput activity. Typically, limited pharmacokinetics studies would be conducted prior to acceptance of a compound for safety evaluation and, as a result, compounds often failed to reach a clinical testing due to unfavorable pharmacokinetic characteristics. A new paradigm in drug discovery has emerged in which the entire sample collection is rapidly screened using robotized high-throughput assays at the outset of the program. Higher-throughput pharmacokinetics (HTPK) is being achieved through introduction of new techniques, including automation for sample preparation and new experimental approaches. A number of in vitro and in vivo methods are being developed for the HTPK. In vitro studies, in which many cell lines are used to screen absorption and metabolism, are generally faster than in vivo screening, and, in this sense, in vitro screening is often considered as a real HTPK. Despite the elegance of the in vitro models, however, in vivo screenings are always essential for the final confirmation. Among these in vivo methods, cassette dosing technique, is believed the methods that is applicable in the screening of pharmacokinetics of many compounds at a time. The widespread use of liquid chromatography (LC) interfaced to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) allowed the feasibility of the cassette dosing technique. Another approach to increase the throughput of in vivo screening of pharmacokinetics is to reduce the number of sample analysis. Two common approaches are used for this purpose. First, samples from identical study designs but that contain different drug candidate can be pooled to produce single set of samples, thus, reducing sample to be analyzed. Second, for a single test compound, serial plasma samples can be pooled to produce a single composite sample for analysis. In this review, we validated the issue whether the second method can be applied to practical screening of in vivo pharmacokinetics using data from seven of our previous bioequivalence studies. For a given drug, equally spaced serial plasma samples were pooled to achieve a 'Pooled Concentration' for the drug. An area under the plasma drug concentration-time curve (AUC) was then calculated theoretically using the pooled concentration and the predicted AUC value was statistically compared with the traditionally calculated AUC value. The comparison revealed that the sample pooling method generated reasonably accurate AUC values when compared with those obtained by the traditional approach. It is especially noteworthy that the accuracy was obtained by the analysis of only one sample instead of analyses of a number of samples that necessitates a significant man-power and time. Thus, we propose the sample pooling method as an alternative to in vivo pharmacokinetic approach in the selection potential lead(s) from combinatorial libraries.

• Korean Journal of Veterinary Research
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• v.38 no.3
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• pp.544-552
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• 1998

A random study of 574 dairy farms in Gyeongnam area was designed to determine 1) management factors that may be associated with the occurrence of drug residues; 2) the dairy farmer's attitudes and knowledge about residues; 3) how these variables influence the occurrence of residues in dairy cattle. Management factors perceived as having the greatest influence on drug residues in milk were insufficient knowledge about withdrawal periods, errors due to hired help, insufficient identification and record of animals treated for mastitis, dry cow treatment for mastitis, and metritis treatment. Seventy-one percent of farms with residues problem used mixed own feeds compared with twenty-nine percent of farms with premedicated feeds. Factors significantly associated with the occurrence of residues were herd size, increased number of hired persons, increased frequency of use of mixed-own feeds, category of medicated feed, and producer's attitude toward the public health significance of residues. Our findings suggest that residue occurrence was mainly associated with errors due to hired help, insufficient knowledge about withdrawal periods, poor animal identification and records of treatment animals and use of medicated feeds. Any residue avodiance educational program needs to stress how to deal with these factors. This educational program should be directed to dairy farmers and employees, especially temporary employees. In addition, Dairy farmer's attitudes and knowledge about drug residues need to be improved. More evidence on the public healths significance of residues should be available to them. Because belife in importance of public healths concerns was related to successful residue avidance and because 81.3% of the dairy farmers with residue problem thought public healths concerns were less important than economic ones, it would be helpful to provide educational programs specifically directed to this issue. it may be useful to provide programs not only for the dairy farmers but also change of their concerns about on the public healths.

• Radiation Oncology Journal
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• v.36 no.4
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• pp.254-264
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• 2018

This article reviewed new trends and controversial issues, including the intensification of chemotherapy and recent brachytherapy (BT) advances, and also reviewed recent consensuses from different societies on the management of locally advanced cervical cancer (LACC). Intensive chemotherapy during and after radiation therapy (RT) was not recommended as a standard treatment due to severe toxicities reported by several studies. The use of positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for pelvic RT planning has increased the clinical utilization of intensity-modulated radiation therapy (IMRT) for the evaluation of pelvic lymph node metastasis and pelvic bone marrow. Recent RT techniques for LACC patients mainly aim to minimize toxicities by sparing the normal bladder and rectum tissues and shortening the overall treatment time by administering a simultaneous integrated boost for metastatic pelvic lymph node in pelvic IMRT followed by MRI-based image guided adaptive BT.

• Korean Journal of Clinical Pharmacy
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• v.31 no.1
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• pp.53-60
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• 2021

Objective: To gather the opinions of hands-on workers for successful introduction of the Development Safety Update Report (DSUR) according to a five-year comprehensive plan for clinical trial development [Ministry of Food and Drug Safety, 2019]. Methods: We conducted a survey on considerations that industry stakeholders may have related to the enforcement of the DSUR. A questionnaire was distributed among pharmacovigilance specialists from 13 pharmaceutical companies in South Korea on June 4, 2020. The questionnaire comprised two sections: 1) current status of the Drug Safety Data Management System and 2) considerations on the implementation and management of the DSUR. Results: All respondents have agreed the introduction of DSUR is inevitable for regulatory harmonization and safety of trial subject. However, most respondents (85%) felt concern about additional workload with DSUR implementation. They answered that format and operation system of DSUR should be harmonized with those of international standards and authorities need to minimize double burden due to related report. Conclusion: All respondents asserted that domestic DSUR should be harmonized with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2F guidelines. Respondents from global companies also suggested regulatory authorities allow DSUR written in English to replace Korean version considering their deadline for submission. Moreover, every respondent agreed regulatory authorities need delicate effort when implementing mandatory submission of DSUR to ensure that even small pharmaceutical companies with no experience in DSUR can comply with the system.

• Journal of Korean Society of Health-System Pharmacists
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• v.35 no.4
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• pp.430-440
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• 2018

Background : Hyponatremia is the most common electrolyte disturbance in hospitalized patients and has been associated with increased morbidity and mortality. Tolvaptan, a vasopressin receptor antagonist, is increasingly used for the treatment of euvolemic and hypervolemic hyponatremia. The aim of this study was to evaluate the effectiveness and safety of tolvaptan for the management of hyponatremia. Methods : This study was a retrospective evaluation of 106 patients who received at least one dose of tolvaptan for hyponatremia at a single tertiary academic hospital between January 2014 and June 2015. The primary endpoint was the change in serum sodium concentration after tolvaptan administration within 24 hours, with secondary endpoints of overcorrection and adverse effects. Results : The mean initial dose of tolvaptan was $20.2{\pm}7.2mg$ and the median duration of treatment was 15 days (range, 1-261 days). The maximal changes in sodium levels at 24 and 48 hours were $8.2{\pm}4.7mmol/L$ and $10.5{\pm}15.3mmol/L$, respectively. Of 99 patients in whom sodium concentrations were followed up, sodium overcorrection was observed in 26 (26.3%) patients, which was associated with concomitant use of an enzyme inhibitor (odds ratio [OR] = 4.80, 95% Cl: 1.27-18.15). However, sex, body mass index (BMI), serum albumin, a daily dose of tolvaptan, and concomitant use of hypertonic saline did not show any significant difference in overcorrection. The most commonly reported adverse effects were mild and related to aquaresis, such as polyuria, thirst, and constipation. However, severe adverse effects such as hyperkalemia, hypotension, and one death related to osmotic demyelination were also reported. Conclusions : Tolvaptan is effective for treating hyponatremia. Nevertheless, the drug should be used cautiously due to serious adverse effects related to sodium overcorrection.

• Journal of Service Research and Studies
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• v.14 no.2
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• pp.48-68
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• 2024

Due to the global pandemic aftermath of the coronavirus, the importance of health care is being emphasized more socially. Due to the influence of these changes, domestic pharmaceutical companies have introduced regular drug delivery services, that is, drug and health functional food subscription services. Currently, this market is continuously growing. However, these regular services are causing new environmental problems in which the number of waste drugs increases due to the presence of unused drugs. Therefore, this study proposes a service that not only promotes health management through regular medication adherence to reduce the amount of pharmaceutical waste but also aims to improve awareness and practices regarding proper medication disposal. As a preliminary survey for service design, a preliminary survey was conducted on 51 adults to confirm their perception of drug use habits and waste drug collection. Based on the Honey Comb model, a guideline for service design was created, and a prototype was produced by specifying the service using the preliminary survey results and service design methodology. In order to verify the effectiveness of the prototype, a first user task survey was conducted to identify the problems of the prototype, and after improving this, a second usability test was conducted on 49 adults to confirm the versatility of the service. Usability verification was conducted using SPSS Mac version 29.0. For the evaluation results of the questionnaire, Spearmann Correlation Analysis was conducted to confirm the relationship between frequency analysis and evaluation items. This study presents specific solutions to the problem of waste drugs due to the spread of drug subscription services.