• Title/Summary/Keyword: crossover analysis

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Bioequivalence of EtodolTM Tablet to KuhnillodineTM Tablet (Micronized Etodolac 200 mg) (건일로딘 정(미결정에토돌락 200 mg)에 대한 에토돌 정의 생물학적동등성)

  • Lee, Jung-Ae;Lee, Yun-Young;Cho, Tae-Seob;Park, Young-Joon;Moon, Byoung-Seok;Kim, Ho-Hyun;Lee, Ye-Rie;Lee, Hee-Joo;Lee, Kyung-Ryul
    • Journal of Pharmaceutical Investigation
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    • v.34 no.4
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    • pp.319-325
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    • 2004
  • A bioequivalence of $Etodol^{TM}$ tablets (Yuhan corporation) and $Kuhnillodine^{TM}$ tablets (Kuhnil Pharm. Co., Ltd.) was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Single 200 mg dose of etodolac of each medicine was administered orally to 24 healthy male volunteers. This study was performed in a $2{\times}2$ crossover design. Concentrations of etodolac in human plasma were monitored by a high-performance liquid chromatography. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 24 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Etodol^{TM}/Kuhnillodine^{TM}$ were 1.01-1.10 and 0.87-1.06, respectively. This study demonstrated a bioequivalence of $Etodol^{TM}$ and $Kuhnillodine^{TM}$ with respect to the rate and extent of absorption.

Bioequivalency and Pharmacokinetics of Two Clarithromycin Tablets (Clarithromycin 정제의 생물학적 동등성 및 약물동태)

  • Kang, Won Ku;Park, Sun Young;Park, Yong Soon;Woo, Jong Su;Choi, Kyung Eob;Kwon, Kwang Il
    • Korean Journal of Clinical Pharmacy
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    • v.9 no.1
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    • pp.49-54
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    • 1999
  • This study was carried out to compare the bioavailability of Hanmi clarithromycin (250 mg/tablet) with that of $Klaricid^{(R)}$ The bioavailability was examined on 20 volunteers who received a single dose (500 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 12 hours. Plasma samples were analyzed for clarithromycin and roxithromycin(internal standard) by HPLC/Coulometric BCD. The pharmaco-kinetic parameters ($AUC_{0-l2hr}$, Cmax, Tmax, $AUC_{inf}$, Ka, Kel, $t_{1/2}$, Vd/F and Cl/F) were calculated from the plasma clarithromycin concentration-time data of each volunteer. The computer program 'WinNonlin' was used for compartmental analysis. One compartment model with first-order input, from order output with lag time, weighting factor $l/y^2$ was chosen as the appropriate pharmacokinetic model. The major pharmacokinetic parameters ($AUC_{0-l2hr},\;AUC_{inf}$, Cmax and Tmax) of Hanmi clarithromycin were $10.7\pm0.5\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;12.7\pm0.7\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;1.7\pm0.1\;{\mu}g/ml\;and\;2.0\pm0.2\;hr$, respectively, and those of $Klaricid^{(R)}\;were\;9.8\pm0.5\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;11.7\pm0.6\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;1.6\pm0.1\;{\mu}g/ml\;and\;2.1\pm0.1\;hr$, respectively. The differences in mean values of $AUC_{0-l2hr},\;AUC_{inf}$ and Cmax between two products were $9.88\%,\;8.94%\;and\;6.59\%$, respectively. The least significant differences at $\alpha=0.05$ for $AUC_{0-l2hr},\;AUC_{inf}$ and Cmax were $16.08\%,\;17.81\%\;and\;18.94\%$, respectively. Though the plasma clarithromycin concentrations of Hanmi clarithromycin were higher than those of $Klaricid^{(R)}$ at all observed times, the bioavailability of Hanmi clarithromycin appeared to be bioequivalent with that of $Klaricid^{(R)}$. The Ka, Kel, $t_{1/2}$, Vd/F and Cl/F of the Hanmi clarithromycin were $2.69\pm0.53\;hr^{-1},\;0.18\pm0.01 hr^{-1},\;3.9\;hr,\;248.8\pm11.4\;L\;and\;43.7\pm2.6\;L/hr$, respectively, and those of $Klaricid^{(R)} were 2.19\pm0.51\;hr^{-1},\;0.18\pm0.02\;hr^{-1},\;3.7\;hr,\;266.7\pm22.4\;L\;and\;45.3\pm2.8L/hr$, respectively. There were no statistically significant differences between two drugs in all pharmacokinetic parameters.

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Bioequivalence and Pharmacokinetics of 70 mg Alendronate Sodium Tablets by Measuring Alendronate in Plasma

  • Yun Min-Hyuk;Woo Jong-Su;Kwon Kwang-Il
    • Archives of Pharmacal Research
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    • v.29 no.4
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    • pp.328-332
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    • 2006
  • The bioequivalence and pharmacokinetics of alendronate sodium tablets were examined by determining the plasma concentration of alendronate. Two groups, consisting of 24 healthy volunteers, each received a 70 mg reference alendronate sodium tablet and a test tablet in a $2{\times}2$ crossover study. There was a 6-day washout period between doses. The plasma alendronate concentration was monitored for 7 h after the dose, using HPLC-Fluorescence Detector (FD). The area under the plasma concentration-time curve from time 0 to the last sampling time at 7 h $(AUC_{0-7h})$ was calculated using the linear-log trapezoidal rule. The maximum plasma drug concentration $(C_{max})$ and the time to reach $C_{max}(T_{max})$ were derived from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed $AUC_{0-7h}\;and\;C_{max}$, and untransformed $T_{max}$. For the test medication versus the reference medication, the $AUC_{0-7h}\;were\;87.63{\pm}29.27\;vs.\;102.44{\pm}69.96ng\;h\;mL^{-1}$ and the $C_{max}$ values were $34.29{\pm}13.77\;vs.\;38.47{\pm}24.39ng\;mL^{-1}$ respectively. The $90\%$ confidence intervals of the mean differences of the logarithmic transformed $AUC_{0-7h}$ and $C_{max}$ values were log 0.8234-log 1.1597 and log 0.8222-log 1.1409, respectively, satisfying the bioequivalence criteria guidelines of both the US Food and Drug Administration and the Korea Food and Drug Administration. The other pharmacokinetic parameters for the test drug versus reference drug, respectively, were: $t_{1/2},\;1.87{\pm}0.62\;vs.\;1.77{\pm}0.54\;h;\;V/F,\;2061.30{\pm}986.49\;vs.\;2576.45{\pm}1826.05\;L;\;CL/F,\;835.32{\pm}357.35\;vs.\;889.48{\pm}485.87\;L\;h^{-1}; K_{el},\;0.42{\pm}0.14\;vs.\;0.40{\pm}0.18\;h^{-1};\;Ka,\;4.46{\pm}3.63\;vs.\;3.80{\pm}3.64\;h^{-1};\;and\;T_{lag},\;0.19{\pm}0.09\;vs.\;0.18{\pm}0.06\;h$. These results indicated that two alendronate formulations(70-mg alendronate sodium) were biologically equivalent and can be prescribed interchangeably.

Comparison of pharmacokinetic characteristics of sildenafil citrate chewable tablets and film-coated tablets in healthy male subjects

  • Yoo, Hyounggyoon;Cho, Sang Min;Choi, Youn Woong;Lee, Hye Jung;Kwon, Ji-Hye;Kim, Soo-Whan;Kim, Jae Woo;Lee, SeungHwan;Hong, Jang-Hee
    • Translational and Clinical Pharmacology
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    • v.25 no.3
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    • pp.153-156
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    • 2017
  • UI14SDF100CW is a chewable tablet of sildenafil citrate, which was developed to improve compliance through convenience of administration. The purpose of this study was to compare the pharmacokinetic (PK) properties of sildenafil citrate chewable tablets (UI14SDF100CW) and conventional sildenafil citrate film-coated tablets ($Viagra^{(R)}$, Pfizer). A randomized, open-label, single dose, two-treatment, two-period, two-way crossover study was conducted in 60 healthy male volunteers. In each period, the subjects received a single oral dose of UI14SDF100CW or $Viagra^{(R)}$ (both tablets contain 140.45 mg of sildenafil citrate, which is equivalent to 100 mg of sildenafil). Serial blood samples were collected up to 24 h post-dose for PK analysis. The plasma concentration of sildenafil was determined using a validated HPLC-MS/MS assay. PK parameters of sildenafil were calculated using non-compartmental methods. The plasma concentration-time profiles of sildenafil in both formulations were similar. For UI14SDF100CW, the $C_{max}$ and $AUC_{last}$ of sildenafil were $1068.69{\pm}458.25$ (mean${\pm}$standard deviation) mg/L and $3580.59{\pm}1680.29h{\cdot}mg/L$, and the corresponding values for $Viagra^{(R)}$ were $1146.84{\pm}501.70mg/L$ and $3406.35{\pm}1452.31h{\cdot}mg/L$, respectively. The geometric mean ratios (90% confidence intervals) of UI14SDF100CW to $Viagra^{(R)}$ for $C_{max}$ and $AUC_{last}$ were 0.933 (0.853-1.021) and 1.034 (0.969-1.108), respectively, which met the bioequivalence criteria of Korean regulatory agency. In conclusion, UI14SDF100CW and $Viagra^{(R)}$ showed similar PK properties. Therefore, UI14SDF100CW can be an alternative to sildenafil for the treatment of erectile dysfunction, providing better compliance.

Development on Metallic Nanoparticles-enhanced Ultrasensitive Sensors for Alkaline Fuel Concentrations (금속 나노입자 도입형의 초고감도 센서 개발 및 알칼라인 연료 측정에 적용 연구)

  • Nde, Dieudonne Tanue;Lee, Ji Won;Lee, Hye Jin
    • Applied Chemistry for Engineering
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    • v.33 no.2
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    • pp.126-132
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    • 2022
  • Alkaline fuel cells using liquid fuels such as hydrazine and ammonia are gaining great attention as a clean and renewable energy solution possibly owing to advantages such as excellent energy density, simple structure, compact size in fuel container, and ease of storage and transportation. However, common shortcomings including cathode flooding, fuel crossover, side yield reactions, and fuel security and toxicity are still challenging issues. Real time monitoring of fuel concentrations integrated into a fuel cell device can help improving fuel cell performance via predicting any loss of fuels used at a cathode for efficient energy production. There have been extensive research efforts made on developing real-time sensing platforms for hydrazine and ammonia. Among these, recent advancements in electrochemical sensors offering high sensitivity and selectivity, easy fabrication, and fast monitoring capability for analysis of hydrazine and ammonia concentrations will be introduced. In particular, research trend on the integration of metallic and metal oxide nanoparticles and also their hybrids with carbon-based nanomaterials into electrochemical sensing platforms for improvement in sensitivity and selectivity will be highlighted.

Orally Administered Korean Herbal Medicine Medications of Randomized Controlled Trials Published in the Journal of Korean Medicine and Related Journals: A Narrative Analysis using CONSORT-CHM 2017 (CONSORT-CHM 2017 지침에 근거한 대한한의학회지 및 회원학회지에 투고된 경구투여 한약 중재를 활용한 무작위 배정 비교 임상 연구(RCT)의 양적, 질적 평가 연구)

  • Se-hun Moon;Jung-ho Jo;Seung-kwan Choi;Yun-hee Han;Hyeon-jun Woo;Byeong-hyeon Jeon;Won-bae Ha;Jung-han Lee
    • The Journal of Internal Korean Medicine
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    • v.44 no.6
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    • pp.1212-1242
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    • 2023
  • Objectives: This study aims to explore the current usage status of orally administered Korean herbal medicine in randomized controlled trials (RCTs) published in the Journal of Korean Medicine and member journals using the CONSORT-Chinese Herbal Medicine Formulas 2017 (CONSORT-CHM 2017) checklist. Methods: We searched the OASIS, RISS, and KMBASE archives as well as the websites of the Journal of Korean Medicine and 45 member journals to identify RCTs that used herbal interventions. Two independent researchers searched and categorized the RCTs and performed a quantitative evaluation by journal, study design, and target disease, as well as qualitative evaluation of the literature using CONSORT-CHM 2017. Results: After the search, 66 articles were selected. The quantitative evaluation resulted in 13 articles (19.6%) that were published in the Journal of Korean Medicine and 12 articles (18.1%) in the Journal of Internal Korean Medicine. In terms of study design, 62 articles (93.9%) were parallel, 4 articles (6%) were crossover, and 2-arm parallel study designs were the most common in 45 articles (68.2%). In terms of the study participants, physiological characteristics and mechanisms in healthy individuals were the most common in 21 studies (31.8%) and obesity in 9 studies (13.6%). In terms of assessing completeness in the CONSORT-CHM 2017 items, 29 articles were rated high, 31 were rated moderate, and 6 were rated low. Items 4a, 6a, and 7a had low reporting rates (≤ 30%), while items 2a, 2b, and 12a were completely reported in all studies. Conclusion: Future RCTs using orally administered Korean herbal medicine need to be reported completely, and the CONSORT-CHM 2017 checklist can be a helpful tool for this purpose.

MRI Evaluation of Suspected Pathologic Fracture at the Extremities from Metastasis: Diagnostic Value of Added Diffusion-Weighted Imaging

  • Sun-Young Park;Min Hee Lee;Ji Young Jeon;Hye Won Chung;Sang Hoon Lee;Myung Jin Shin
    • Korean Journal of Radiology
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    • v.20 no.5
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    • pp.812-822
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    • 2019
  • Objective: To assess the diagnostic value of combining diffusion-weighted imaging (DWI) with conventional magnetic resonance imaging (MRI) for differentiating between pathologic and traumatic fractures at extremities from metastasis. Materials and Methods: Institutional Review Board approved this retrospective study and informed consent was waived. This study included 49 patients each with pathologic and traumatic fractures at extremities. The patients underwent conventional MRI combined with DWI. For qualitative analysis, two radiologists (R1 and R2) independently reviewed three imaging sets with a crossover design using a 5-point scale and a 3-scale confidence level: DWI plus non-enhanced MRI (NEMR; DW set), NEMR plus contrast-enhanced fat-saturated T1-weighted imaging (CEFST1; CE set), and DWI plus NEMR plus CEFST1 (combined set). McNemar's test was used to compare the diagnostic performances among three sets and perform subgroup analyses (single vs. multiple bone abnormality, absence/presence of extra-osseous mass, and bone enhancement at fracture margin). Results: Compared to the CE set, the combined set showed improved diagnostic accuracy (R1, 84.7 vs. 95.9%; R2, 91.8 vs. 95.9%, p < 0.05) and specificity (R1, 71.4% vs. 93.9%, p < 0.005; R2, 85.7% vs. 98%, p = 0.07), with no difference in sensitivities (p > 0.05). In cases of absent extra-osseous soft tissue mass and present fracture site enhancement, the combined set showed improved accuracy (R1, 82.9-84.4% vs. 95.6-96.3%, p < 0.05; R2, 90.2-91.1% vs. 95.1-95.6%, p < 0.05) and specificity (R1, 68.3-72.9% vs. 92.7-95.8%, p < 0.005; R2, 83.0-85.4% vs. 97.6-98.0%, p = 0.07). Conclusion: Combining DWI with conventional MRI improved the diagnostic accuracy and specificity while retaining sensitivity for differentiating between pathologic and traumatic fractures from metastasis at extremities.

Changes in Occupational Therapy Students' Occupational Balance and Quality of Life in Epidemic of COVID-19 (COVID-19 유행으로 인한 작업치료(학)과 학생들의 작업균형과 삶의 질 변화)

  • Lee, Hyang-sook;Han, Gyeong-ju;Park, In-yeong;Hwang, Eun-bi;Chae, Hyun-ah;Noh, Chong-su;Cha, Jung-jin
    • The Journal of Korean society of community based occupational therapy
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    • v.11 no.1
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    • pp.11-22
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    • 2021
  • Objective : The purpose of this study was to investigate the changes in occupational balance and quality of life caused by COVID-19 in occupational therapy students. Methods : From May 27 to June 26, 2020, questionnaires were distributed to a total of 35 universities among 62 occupational therapy departments nationwide. General characteristics, COVID-19 related characteristics, OBQ and WHOQOL-BREF were used to evaluate and analyze occupational balance and quality of life. The SPSS/PC 24.0 program was used to analyze frequency analysis, crossover analysis, chi-square test, independent t-test, analysis of variance, and Pearson correlation analysis. Results : There were significant differences in school system(years), class, life pattern, quality of life, personal and public schedule depending on whether they are interested in occupational balance. There were significant differences in occupational balance(OBQ) and quality of life(WHOQOL-BREF), 'Hobby', 'new hobbies after COVID-19', 'life patterns', 'use of public transportation', 'maintenance of occupational balance', and 'quality of life'. There was a significant positive correlation occupational balance and quality of life. Conclusion : This study showed that the more people who have changed their lives due to COVID-19 are interested in work balance, and the better they maintain their work balance and emotional well-being, the higher the work balance and quality of life, and the positive correlation between work balance and quality of life was confirmed. This will be the basis for studies related to intervention strategies that can improve occupational balance and quality of life in a time when social isolation is easy due to the COVID-19 epidemic.

Analysis of Coexistence Rates of Attention Deficit/Hyperactivity Disorder Symptoms in Patients with Depression (우울감을 주소로 내원한 환자들에서 주의력 결핍/과잉행동장애 증상의 공존율 분석)

  • Jeong, Mi Young;Park, Seo Young;Kim, Jung Ho;Im, Woo Young;Lee, Yeon Jung
    • Korean Journal of Psychosomatic Medicine
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    • v.27 no.2
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    • pp.147-154
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    • 2019
  • Objectives : Cognitive dysfunction, including inattention, is often observed in patients with depression. Inattentive symptoms in patients with depression is similar to those among attention deficit/hyperactivity disorder (ADHD) patients. It is important to diagnose the two diseases accurately, because the treatment varies depending on the cause of inattention. This study aimed to investigate the coexistence rate of ADHD and the correlation between ADHD symptoms and depression in patients with depression. Methods : Participants in this study were 158 outpatients presenting with depression, who visited the psychiatric department from March 2015 to July 2018. Participants divided into a depression and a non-depression group according to the Korean version of the Center for Epidemiological Studies-Depression Scale (CES-D) score and were administered the following : a sociodemographic variables form (age, sex, academic background, occupation), the self-reporting test for adult ADHD (Adult Attention Deficit/Hyperactivity Disorder self-report scale-V 1.1; ASRS V1.1), and the Korean version of the Connors adult ADHD rating scale (K-CAARS). Descriptive statistical analysis, crossover analysis, t-tests, and Pearson's correlation coefficient were conducted on the data. Results : The coexistence rate of adult ADHD symptom was as high as 36.7% in patients with depression (p<0.001). In K-CAARS, the depression group (Inattention=1.80, Hyperactivity=1.92, Impulsivity=1.56, Self-concept=2.06) showed higher average scores on ADHD symptoms than the non-depressive group (Inattention=1.28, Hyperactivity=1.25, Impulsivity=1.09, Self-concept=1.42, p<0.001). Conclusions : This study confirmed that ADHD symptoms coexist in the depression group. When evaluating the symptoms of patients who complain of depression, it is suggested that they should be accurately diagnosed and appropriately treated with interest to the coexistence of ADHD symptoms and the possibility for ADHD diagnosis.

Optimization of Multiclass Support Vector Machine using Genetic Algorithm: Application to the Prediction of Corporate Credit Rating (유전자 알고리즘을 이용한 다분류 SVM의 최적화: 기업신용등급 예측에의 응용)

  • Ahn, Hyunchul
    • Information Systems Review
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    • v.16 no.3
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    • pp.161-177
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    • 2014
  • Corporate credit rating assessment consists of complicated processes in which various factors describing a company are taken into consideration. Such assessment is known to be very expensive since domain experts should be employed to assess the ratings. As a result, the data-driven corporate credit rating prediction using statistical and artificial intelligence (AI) techniques has received considerable attention from researchers and practitioners. In particular, statistical methods such as multiple discriminant analysis (MDA) and multinomial logistic regression analysis (MLOGIT), and AI methods including case-based reasoning (CBR), artificial neural network (ANN), and multiclass support vector machine (MSVM) have been applied to corporate credit rating.2) Among them, MSVM has recently become popular because of its robustness and high prediction accuracy. In this study, we propose a novel optimized MSVM model, and appy it to corporate credit rating prediction in order to enhance the accuracy. Our model, named 'GAMSVM (Genetic Algorithm-optimized Multiclass Support Vector Machine),' is designed to simultaneously optimize the kernel parameters and the feature subset selection. Prior studies like Lorena and de Carvalho (2008), and Chatterjee (2013) show that proper kernel parameters may improve the performance of MSVMs. Also, the results from the studies such as Shieh and Yang (2008) and Chatterjee (2013) imply that appropriate feature selection may lead to higher prediction accuracy. Based on these prior studies, we propose to apply GAMSVM to corporate credit rating prediction. As a tool for optimizing the kernel parameters and the feature subset selection, we suggest genetic algorithm (GA). GA is known as an efficient and effective search method that attempts to simulate the biological evolution phenomenon. By applying genetic operations such as selection, crossover, and mutation, it is designed to gradually improve the search results. Especially, mutation operator prevents GA from falling into the local optima, thus we can find the globally optimal or near-optimal solution using it. GA has popularly been applied to search optimal parameters or feature subset selections of AI techniques including MSVM. With these reasons, we also adopt GA as an optimization tool. To empirically validate the usefulness of GAMSVM, we applied it to a real-world case of credit rating in Korea. Our application is in bond rating, which is the most frequently studied area of credit rating for specific debt issues or other financial obligations. The experimental dataset was collected from a large credit rating company in South Korea. It contained 39 financial ratios of 1,295 companies in the manufacturing industry, and their credit ratings. Using various statistical methods including the one-way ANOVA and the stepwise MDA, we selected 14 financial ratios as the candidate independent variables. The dependent variable, i.e. credit rating, was labeled as four classes: 1(A1); 2(A2); 3(A3); 4(B and C). 80 percent of total data for each class was used for training, and remaining 20 percent was used for validation. And, to overcome small sample size, we applied five-fold cross validation to our dataset. In order to examine the competitiveness of the proposed model, we also experimented several comparative models including MDA, MLOGIT, CBR, ANN and MSVM. In case of MSVM, we adopted One-Against-One (OAO) and DAGSVM (Directed Acyclic Graph SVM) approaches because they are known to be the most accurate approaches among various MSVM approaches. GAMSVM was implemented using LIBSVM-an open-source software, and Evolver 5.5-a commercial software enables GA. Other comparative models were experimented using various statistical and AI packages such as SPSS for Windows, Neuroshell, and Microsoft Excel VBA (Visual Basic for Applications). Experimental results showed that the proposed model-GAMSVM-outperformed all the competitive models. In addition, the model was found to use less independent variables, but to show higher accuracy. In our experiments, five variables such as X7 (total debt), X9 (sales per employee), X13 (years after founded), X15 (accumulated earning to total asset), and X39 (the index related to the cash flows from operating activity) were found to be the most important factors in predicting the corporate credit ratings. However, the values of the finally selected kernel parameters were found to be almost same among the data subsets. To examine whether the predictive performance of GAMSVM was significantly greater than those of other models, we used the McNemar test. As a result, we found that GAMSVM was better than MDA, MLOGIT, CBR, and ANN at the 1% significance level, and better than OAO and DAGSVM at the 5% significance level.