• Journal of Pharmaceutical Investigation
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• v.21 no.1
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• pp.23-32
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• 1991

Dissolution profiles of ketoconazole in solid dispersion system (SDS) were investigated in the second fluid (pH 6.8) for the dissolution test (KPV). PVP K-30 and methyl cellulose were used as carriers in SDS, and chloroform as a solvent. Computer optimization technique was applied to obtain an optimum formula of SDS, and the following results were obtained; 1) Dissolution rate of ketoconazole in SDS was larger than that of pure ketoconazole in the second fluid of pH 6.8. 2) PVP K-30 and methyl cellulosr were good carriers for SDS of ketoconazole. Moerover PVP K-30 was better than methyl cellulose. 3) The optimum formula of ketoconazole SDS obtained from computer optimization technique was chloroform 175 ml, PVP K-30 5g and methyl cellulose 0.2g per 1g of ketoconazole. 4) The experimental value of $A_{60}$ (Amount released from ketoconazole tablet during 60 minutes) obtained from SDS by optimum formula agreed well with the value calculated by polynomial regression equation.

• The Journal of the Korean Society for Microbiology
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• v.21 no.1
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• pp.63-71
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• 1986

The antifungal activities of amphotericin B, 5-fluorocytosine, and ketoconazole in combination of amphotericin B/ketoconazole and 5-fluorocytosine/ketoconazole were determined against 42 strains of Candida spp. isolated from oral cavity. Among 42 strains of Candida species, 36 strains of Candida albicans, 2 strains of Candida parapsilosis and Candida tropicalis 1 strain of Candida krusei and Candida stellatoidea were identified. The minimum inhibitory concentrations(MICs) of amphotericin B, 5-fluorocytosine and ketoconazole for these strains were ranged from 0.05-1.56 mcg/ml, 12.5->100.0 mcg/ml and 0.2-50.0 mcg/ml. In all of the experimental strains, amphotericin B had the greatest antifungal activity on a dilution basis. When a microtiter checkerboard technique was used 5-fluorocytosine acted synergistically with ketoconazole against all strains, whereas amphotericin B has a reduced effect. The killing curve experiments with on strain of Candida albicans WMC-85024 demonstrated that the combination of amphotericin B/ketoconazole and 5-fluorocytosine/ketoconazole produced a decrease in number of colony forming unit of >3 logs in 72 hours.

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.241-247
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• 1998

Ketoconazole is an imidazole antifungal agent which inhibits the biosynthesis of fungal cellmembrane ergosterol and has immunosuppressive properties in vitro. Biphenyl dimethyl dicarboxylate (PMC) has been utilized for antioxidative action and for liver-protective purposes. Studies were undertaken to investigate effects of biphenyl dimethyl dicarboxylate (PMC) on the immunosuppression of ketoconazole in ICR mice. In the combination of PMC and ketoconazole, as compared with the treatment of ketoconazole alone, there were significant increases in activities of natural killer (NK) cells and phagocytes along with circulation leukocytes. The elevation of serum glutamic-pyruvic transaminase (S-GPT) and total protein levels caused by ketoconazole were reduced by the combination of PMC and ketoconazole. In addition, lower serum albumin and albumin/globulin (A/G) ratio were also increased to normal level.

• Journal of Pharmaceutical Investigation
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• v.33 no.3
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• pp.223-227
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• 2003

The purpose of this study was to investigate the effect of ketoconazole (20 mg/kg) on the pharmacokinetic parameters and the bioavailability of paclitaxel (40 mg/kg) orally coadministered in rats. The plasma concentration of paclitaxel in combination with ketoconazole was significantly (p<0.05) increased from 8 hr to 24 hr compared to that of control. Area under the plasma concentration-time curve (AUC) of paclitaxel with ketoconazole was significantly (coadministration p<0.05, pretreatment p<0.0l) higher than that of control. Peak concentration $(C_{max})$ of paclitaxel pretreated with ketoconazole were significantly (p<0.05) increased compared to that of control. Time to peak concentation $(T_{max})$ of paclitaxel pretreated with ketoconazole were significantly (p<0.05) shorter than that of control. Half-life at elimination phase $(t_{1/2{\beta}})$ of paclitaxel pretreated with ketoconazole was significantly (p<0.05) prolonged compared to that of control. Based on these results, it might be due to both inhibition of the enzyme cytochrome P450 and p-glycoprotein, which engaged in paclitaxel absorption and metabolism in liver and gastrointestinal mucosa.

• Archives of Pharmacal Research
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• v.27 no.3
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• pp.295-299
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• 2004

The antifungal activities of the essential oil from Agastache rugosa and its main component, estragole, combined with ketoconazole, one of the azole antibiotics commonly used to treat infections caused by Trichophyton species, were evaluated in this study. The combined effects were measured by the checkerboard microtiter and the disk diffusion tests, against T. erinacei, T. mentagrophytes, T. rubrum, T. schoenleinii and T. soudanense. Susceptibility of the five Trichophyton species to the oil alone, or ketoconazole alone, differed distinctly. The fractional inhibitory concentration indices (FICI) of ketoconazole combined with estragole or A. rugosa essential oil, against the tested Trichophyton species, were between 0.05 and 0.27, indicating synergistic effects. These drug combinations exhibited the most significant synergism against T. mentagrophytes, with FICIs of 0.05 and 0.09 for estragole and the essential oil fraction from A. rugosa, respectively. Isobolograms based on the data from checkerboard titer tests also indicated significant synergism between ketoconazole and the Agastache oil fraction or estragole, against the Trichophyton species evaluated. Trichophyton susceptibility to ketoconazole was significantly improved by combination with the Agastache rugosa oil fraction or its main component, estragole.

• Natural Product Sciences
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• v.14 no.1
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• pp.27-31
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• 2008

We have evaluated the combined antifungal effects of the essential oil from Eucalyptus globulus or its main component 1,8-cineole with ketoconazole. Checkerboard microtiter tests were used to analyze their effects against three Candida and six Trichophyton species. The susceptibility of the Trichophyton species to E. globulus essential oil differed distinctly. The fractional inhibitory concentration indices (FICIs) against the tested Candida species ranged between 0.09 and 0.38 for ketoconazole combined with E. globulus essential oil or 1,8-cineole, indicating significant synergism between ketoconazole and the oil samples. Similar experiments using Trichophyton species resulted in FICIs between 0.28 and 0.63, indicating relatively weaker combined effects than those observed with Candida species. Thus, the data reported here show that the anti-Candida effects of ketoconazole can be significantly improved in the presence of E. globulus essential oil or 1, 8-cineole.

• Korean Journal of Veterinary Research
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• v.45 no.2
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• pp.255-261
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• 2005

The purpose of this study is to compare hepatotoxicity of each treatment for dermatophytosis; one is the administration of the ketoconazole only and the other, ketoconazole with diphenyl-dimeththyl-dicarboxylate. Have chosen the range of 14-24 months of healthy dogs divided by two groups (group 1 and group 2) for the experiment of which test proved positive in dermatophytosis diagnosis and showed normal reaction in terms of physical examination, blood chemistry and especially of liver function. Group 1 was administrated ketoconazole orally at 10 mg/kg/day and of same dose of ketoconazole with diphenyl-dimethyl-dicarboxylate for group 2. After administering, we have tested two groups by blood collecting every one week in order to check the differences of hepatotoxicity state through AST, ALT and r-GTP, the barometers of liver function which lasted for 12 weeks. Moreover, tested Indocyanine Green (ICG), known as susceptible gauge of function of excretion before starting the experiment and tested ICG as well after 12 weeks. The experiment of result the value of group 1 in AST, ALT and r-GTP has been highly rised after administering ketoconazole for 10 weeks meanwhile, of group 2 has shown a steady state troughout the whole experiment. For ICG test, we injected 0.5 mg/kg of ICG into a vein for both groups and tested the retention rate at regular interval of 15, 30, 45 minutes. The results of retention rate in two groups were similar to before the drug administration. However, after 12 weeks the retention rate of group 1 has been delayed, on the other hand, retention rate of group 2 were a steady state. In conclusion, the administration of ketoconazole only for a long period of time induced hepatotoxicity where as, the administration of ketoconazole with diphenyl-dimethyl-dicarboxylate didn't induce hepatotoxicity. Therefore, when doctors prescribes for a dog with dermatophytosis should not administrate ketoconnazole itself but with diphenyl-dimethyl-dicarboxylate and one who has abnormal condition of liver function should not be prescribed ketoconazole treatment. If there is a case needed to prescribe ketoconazole treatment, the regular monitoring should be accompanied by at the same time.

• Journal of Microbiology and Biotechnology
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• v.28 no.11
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• pp.1937-1945
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• 2018

Malassezia pachydermatis is a commensal yeast found on the skin of dogs. However, M. pachydermatis is also considered an opportunistic pathogen and is associated with various canine skin diseases including otitis externa and atopic dermatitis, which usually require treatment using an azole antifungal drug, such as ketoconazole. In this study, we isolated a ketoconazole-resistant strain of M. pachydermatis, designated "KCTC 27587," from the external ear canal of a dog with otitis externa and analyzed its resistance mechanism. To understand the mechanism underlying ketoconazole resistance of the clinical isolate M. pachydermatis KCTC 27587, the whole genome of the yeast was sequenced using the PacBio platform and was compared with M. pachydermatis type strain CBS 1879. We found that a ~84-kb region in chromosome 4 of M. pachydermatis KCTC 27587 was tandemly quadruplicated. The quadruplicated region contains 52 protein coding genes, including the homologs of ERG4 and ERG11, whose overexpression is known to be associated with azole resistance. Our data suggest that the quadruplication of the ~84-kb region may be the cause of the ketoconazole resistance in M. pachydermatis KCTC 27587.

• Journal of Powder Materials
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• v.30 no.6
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• pp.493-501
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• 2023

This study aimed to develop a solid self-nanoemulsifying drug delivery system (solid-SNEDDS) to enhance the formulation of ketoconazole (KTZ), a BCS Class II drug with poor solubility. Ketoconazole, which is insoluble above pH 3, requires solubilization for effective delivery. This SNEDDS comprises oil, surfactant, and co-surfactant, which spontaneously emulsify in the gastrointestinal tract environment to form nanoemulsions with droplet sizes less than 100 nm. The optimal SNE-vehicle composition of oleic acid, TPGS, and PEG 400 at a 10:80:10 weight ratio was determined based on the smallest droplet size achieved. This composition was used to prepare liquid SNEDDS containing ketoconazole. The droplet size and polydispersity index (PDI) of the resulting liquid SNEDDS were analyzed. Subsequently, solid-SNEDDS was fabricated using a spray-drying method with solidifying carriers such as silicon dioxide, crospovidone, and magnesium alumetasilicate. The physicochemical properties of the solid-SNEDDS were characterized by scanning electron microscopy and powder X-ray diffraction, and its solubility, droplet size, and PDI were evaluated. In particular, the solid-SNEDDS containing ketoconazole and crospovidone in a 2:1 weight ratio exhibited significantly enhanced solubility, highlighting its potential for improved medication adherence and dissolution rates.

• Biomedical Science Letters
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• v.3 no.1
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• pp.49-54
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• 1997

Meanwhile Pityrosporum species as well as Candida species in yeast phase are not pathogenic, Pityrosporum in mycelial phase is pathogenic. Pityrosporum species can be isolated not only from tinea versicolor patients but also from ninety (90) percent of healthy persons. Minimal inhibitory concentration (MIC) of ketoconazole against Pityrosporum spp. was 0.05~0.8$\mu\textrm{g}$ ml$^{-1}$and the MIC of ketoconazole was the lowest. Of itraconazole, selenium sulfide, sodium thiosulfate and ketoconazole had the lowest MIC against P. orbiculare. The P. orbiculare strains isolated from healthy persons were inhibited by lower MIC than those isolated from tinea versicolor patients. P. ovale strains were inhibited by lower MIC at MIC$_{50}$ and MIC$_{90}$ of oral and topical antifungal agents than p. orbiculare.