• Journal of Pharmaceutical Investigation
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• v.24 no.2
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• pp.85-94
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• 1994

Inclusion complexes of ketoconazole (KT) with ${\alpha}-$, ${\beta}-cyclodextrin$ (CD) and dimethyl-${\beta}-cyclodextrin$ $(DM{\beta}CD)$ in a molar ratio of 1:2 were prepared by freeze-drying and solvent evaporation methods. The interactions of KT with ${\alpha}-CD$, ${\beta}-CD$ and $DM{\beta}CD$ in aqueous solution and in solid state were investigated by solubility study, infrared (lR) spectroscopy and differential scanning calorimetry (DSC). The stability constant of $KT-DM{\beta}CD$ inclusion complex (lC) was found to be the largest among three inclusion complexes. Clear differences in IR spectra and DSC curves were observed between inclusion complexes and physical mixtures (PM) of KT-CDs. It was also shown by IR spectra and DSC curves that solvent evaporation method might be. superior to the freeze-drying method in preparing the inclusion complexes of KT-CDs. The dissolution rate of KT was markedly increased by inclusion complex formation with CDs in the buffer solution at pH 4.0 and pH 6.8. The mean dissolution time (MDT,min), which represents the rapidity of dissolution, was in the order of $KT-DM{\beta}CD$ IC (3.20) < $KT-{\beta}-CD$ IC (4.36) < $KT-{\alpha}-CD$ IC (6.99) < $KT-{\alpha}-CD$ PM (17.46)< $KT-{\beta}-CD$ PM (19.36) < $KT-{\beta}-CD$ PM (28.53). The dissolution rates of KT-CD ICsprepared by solvent evaporation method were faster than those of KT-CD ICs prepared by freeze-drying method.

• YAKHAK HOEJI
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• v.40 no.1
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• pp.90-94
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• 1996

6-[(N-4-Fluorophenyl)amino]-7-chloro-5,8-quinolinedione(RCK3) was tested for antifungal activities, in vivo, against Candida albicans. RCK3 was compared with ketoc onazole and fluconazole in the treatment of systemic infection with Candida albicans in normal mice. The therapeutic potential of RCK3 had been assessed by evaluating their activities (survival rate) against systemic infections in normal mice. RCK3 had $ED_{50},\;8.78{\pm}0.18mg/kg$ but ketoconazole and fluconazole had $ED_{50},\;8.00{\pm}0.73,\;10.00{\pm}0.43mg/kg$ respectively. Intraperitoneally administered RCK3 at the $ED_{50}$, 8.78mg/kg for 7 days and 14 days reduced Candida albicans colony count in the kidneys and livers as well as ketoconazole and fluconazole at these $ED_{50}$, 8.00 and 10.00mg/kg. And administered RCK3 at the $ED_{50}$ for 14 days improved survival rates better than ketoconazole.

• The Journal of the Korean Society for Microbiology
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• v.22 no.3
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• pp.301-307
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• 1987

A total of 42 strains of Candida albicans were examined for susceptibility to three antifungal agents, amphotericin B(AMB), 5-fluorocytosine(5-FC), and ketoconazole(KTZ), using defined medium, synthetic amino acid medium-fungal(SAAM-F), supplemented yeast nitrogen base(SYNB) and undefined medium Sabouraud's dextrose broth(SDB) and Kimmig broth media. A tube dilution method was used with minimum inhibitory concentrations(MICs) determined after incubation for 24 hour and 48 hours. All testes were performed in duplicate. In general, MICs were more reproducible after 48 hour of incubation. Forthermore, MICs determined after incubation for 48 hours were significantly higher than those determined after 24 hours. The actural MICs obtained with the different antifungal agents were clearly influenced by the test medium used. The rank order of AMB MICs according to the test medium was as follows: SAAM-F>SYNB>SDB>Kimmig broth. With 5-FC, the following pattern was observed: SYNB>SAAM-F>SDB>Kimmig borth. For ketoconazole, the MICs according to the test medium was SAAM-F>SDB>SYNB> Kimmig broth. In amphotericin B, the MICs mean value with the test medium was as follows: SDB, 0.24 mcg/ml; Kimmig broth, 0.29 mcg/ml; SYNB, 0.21 mcg/ml and SAAM-F, 0.15mcg/ml. The actural value of 5-FC was; SDB, 37.20 mcg/ml; Kimmig broth, 67.41mcg/ml; SYNB, 21.29 mcg/ml and SAAM-F, 24.61 mcg/ml and in ketoconazole, the MICs value was; SDB, 1.83 mcg/ml; Kimmig broth, 4.08 mcg/ml; SYNB, 1.95 mcg/ml and SAAM-F, 1.41 mcg/ml. The results of this investigation suggested that broth dilution susceptibility testing of yeast and yeast-like fungi are best performed with an incubation period of 48 hours. Furthermore, medium composition can significantly influence the results of such testing.

• Journal of Veterinary Science
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• v.22 no.1
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• pp.4.1-4.13
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• 2021

Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood. The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis. The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions: The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

• YAKHAK HOEJI
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• v.40 no.5
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• pp.608-615
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• 1996

6-[(N-3,4-Difluorophenyl)amino]-7-chloro-5,8-quinolinedione(RCK4) was tested for antifungal activities, against systemic infections with Candida albicans in normal mice. The therapeutic potential of RCK4 had been assessed in comparison with ketoconazole and fluconazole. RCK4 had $ED_{50},\;0.30{\pm}0.14$ but ketoconazole and fluconazole had $ED_{50},\;8.00{\pm}0.73,\;10.00{\pm} 0.43mg/kg$ respectively. Intraperitoneally administered RCK3 at the $ED_{50}$ for 7 days and 14 days reduced Candida albicans colony count in the kidneys and liver as well as ketoconazole and fluconazole at these $ED_{50}$. And administered RCK4 at the $ED_{50}$ for 14 days improved survival rates as well as ketoconazole. Acute oral toxicity studies of RCK4 were carried out in ICR mice of both sexes. These acute oral toxicities of RCK4 were low and $LD_{50}$ values were over 2,850mg/kg in ICR mice. The genotoxicities of RCK4 had been evaluated. RCK4 was negative in Ames test with Salmonella typhimurium and chromosomal aberration test in CHL cells. The clastogenicity was tested on the RCK4 with in vivo mouse micronucleus assay. RCK4 did not show any clastogenic effect in mouse peripheral blood and was negative in mouse micronucleus assay. These results indicate that RCK4 has no genotoxic potential under these experimental conditions.

• Journal of Veterinary Clinics
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• v.18 no.1
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• pp.1-6
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• 2001

The aim of this study was to determine optimal therapeutic dose of antifungal agents for dermatophytes. Forty nine dermatophytes were isolated form dogs and cats showing skin lesions and were tested for their in vitro susceptibility to nystatin, griseofulvin, terbinafine, ketoconazole and fluconazole by broth microdilution test. Terbinafine showed the lowest MIC value among the antifungal agents tested, and MIC values ranged from 0.002 to 0.016 $\mu\textrm{g}$/ml. Fluconazole showed the highest MIC values among the antifungal agents tested, and MIC values ranged from 32 to 512 $\mu\textrm{g}$/ml. MIC values of nystatin, griseofulvin and ketoconazole ranged from 1.12 to 4.48 $\mu\textrm{g}$/ml, 0.5 to 4.0 $\mu\textrm{g}$/ml, and 1.6 to 12.8 $\mu\textrm{g}$/ml, resistant to griseofulvin, and that antifungal susceptibility test was needed to determine optimal therapeutic dose of antifungal agents for each dermatophyte.

• The Korean Journal of Mycology
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• v.25 no.4 s.83
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• pp.348-353
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• 1997

Ether extract of Cinnamomi Cortex showing antifungal activity was purified and characterized. The active component from the extract was identified to be trans-cinnamaldehyde, which was effective in inhibiting the growth of the representative fungi of dermatomycosis with minimum inhibitory concentration of $39{\sim}78\;{\mu}g/ml$. The antifungal spectrum of trans-cinnamaldehyde was broader than that of commercial antifungal agent, Ketoconazole.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.128-128
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• 2002

In association with the international validation project to establish a test protocol for the "Enhanced OECD Test Guideline 407", we performed a 28-day repeated-dose toxicity study of vinclozolin (VCZ), an androgen antagonist, and ketoconazole (KCZ), a biosynthesis inhibitor of testosterone (T), and assessed the sensitivity of new parameters for detecting endocrine-related effects of endocrine-disrupting chemicals.(omitted)

• The Journal of Korean Medicine
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• v.20 no.1 s.37
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• pp.22-29
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• 1999

To evaluate the effect of Choakwiyeum water extract on the male reproductive functions, experiments were performed on male rats. The results obtained were as follows: 1. Intromission frequency was increased significantly after the administration of Choakwiyeum water extract in male rats. 2. Intromission latency was increased significantly after the administration of Choakwiyeum water extract and ketoconazole in male rats. 3. Mount frequency was increased significantly after the administration of Cboakwiyeum water extract and TCDD in male rats. 4. Serum testosterone concentration was increased significantly after the administration of Choakwiyeum water extract in male rats. 5. Serum testosterone concentration was increased significantly after the administration of Choakwiyeum water extract and ketoconazole in male rats.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.24 no.1
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• pp.100-112
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• 1998

향 비듬 샴푸에 대한 비중이 증가되는 현 샴푸시장에서 향 비듬력을 측정할 수 있는 간단한 in vitro 실험법의 요구가 증대되고 있다. 기존의 향 비듬력의 측정을 위하여 사용되고 있는 방법으로는 Pityrosporum ovale에 대한 MIC test와 halo test가 널리 쓰이고 있으나, Pityrosporum 배지의 자체 탁도 때문에 균의 성장 여부를 육안으로 관찰하기 어렵고, 종이 디스크와 두피와의 차이에 의하여 실제 사용과 효과가 다르다는 단점이 있었다. 저자들은 임상 실험을 거치기 전 간단히 향 비듬력을 측정할 수 있는 in vitro 방법으로 skin disk diffusion method를 개발하였다. SDDM에서는 종이 디스크 대신 기니픽의 피부 조직을 사용하고, 향 비듬 제제의 처리 후 세척 단계를 포함시켜 실제 사용과의 차이를 줄였다. SDDM의 유용성을 확인하기 위하여 향 비듬 제제로 2.0% ketoconazole, 분산된 상태의 zinc pyrithion, 분자화 기술로 활성을 높인 ZPT에 대해 기존의 in vitro 시험법과 함께 향 비듬력을 측정하였다. 결과는 SDDM 시험에서만 20% ketoconazole 제제와 분자화된 0.5% ZPT제제의 억제대가 비슷한 것으로 나타나 임상 시험에서 두 제제 모두 비듬에 대해 개선 효과가 있었으며 향 비듬 효과에 차이가 없다는 결과와 일치하였다. 본 시험의 결과로 SDDM이 향 비듬 샴푸와 같은 wash-off 제품의 효능 측정에 간단하고 효과적인 적절한 in vitro 시험법으로 생각되어 SDDM 시험과 임상 시험결과를 소개한다.