• Journal of Pharmaceutical Investigation
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• v.32 no.4
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• pp.299-303
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• 2002

The oral bioavailability of itraconazole is variable and low in fasting state. This is mainly due to the low solubility of this drug. Bioavailability can be improved by changing the formulation and it is general that the liquid preparations show greater bioavailability than the solid dosage forms such as tablets and capsules do. Benzyl alcohol-water binary mixture showed the excellent solubilizing capacity for itraconazole but the release of the drug from the preparation needs to be enhanced. In this study, various nonionic surfactants and hydrophilic polymers, poloxamers, were screened to investigate their effects on the releasε of itraconazole from the liquid preparations. Poloxamer 407 showed the most enhancing effect on the drug release and the release rate was proportional to thε amount of poloxamer 407 added. A liquid preparation of itraconazole, consisting of benzyl alcohol/water/poloxamer 407 ternary solvent system, releasεd more than 80% of the total drug amount at 5 min and showεd the possibility of a new formulation development.

• Korean Journal of Clinical Pharmacy
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• v.26 no.4
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• pp.306-311
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• 2016

Objective: This study was performed to compare the changes in the blood concentrations of tacrolimus when either itraconazole or voriconazole is together with tacrolimus to prevent or treat invasive aspergillus pneumonia (IAP) in patients with lung transplants. Therefore we can compare the degree of drug-drug interactions between tacrolimus and itraconazole against tacrolimus and voriconazole. Methods: Patients who were admitted and had lung transplants in a territory referral hospital from September 2012 to May 2015 were analyzed retrospectively. The effects of itraconazole and voriconazole on the plasma concentrations of tacrolimus were analyzed. Results: Mean tacrolimus concentrations was $10.49{\pm}2.35ng/mL$ vs. $10.95{\pm}2.98ng/mL$ (p=0.722), and mean concentration of tacrolimus over the dose of tacrolimus per day was $8.510{\pm}5.890(ng/mL)/(mg/d)$ vs. $15.45{\pm}28.47(ng/mL)/(mg/d)$ (p=0.947) in itraconazole vs. voriconazole group each. The ratio of the number of the results out of target tacrolimus concentrations to the total number of tacrolimus concentration results was $18.0{\pm}13.3%$ vs. $24.4{\pm}18.5%$ (p=0.185). Conclusion: There were no significant differences between itraconzaole and voriconazole to have influences on mean concentrations of tacrolimus over tacrolimus dose per weight per day. However voriconazole tended to raise tacrolimus plasma concentrations more than itraconazole. Safer and more effective drug management to prevent and treat fungal infections should be done by therapeutic drug monitoring not only of tacrolimus but of itraconazole and voriconazole in lung transplant patients.

• Journal of Veterinary Clinics
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• v.21 no.2
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• pp.209-213
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• 2004

A 8 kg, 3-year-old male West Highland white terrier dog with a 1.5-year history of chronic, severely pruritic, seborrheic skin disorder was referred to the Veterinary Medical Teaching Hospital of the Tokyo University of Agriculture and Technology. On physical examination, lesions were observed on entire cutaneous surface, except for face, dorsum of body, and footpads. Skin lesions were characterized by diffuse erythema, erythematous papules, severe alopecia, hyperpigmentation, and lichenification. Tape strip tests of skin lesions revealed cocci and Malassezia infections. The intradermal allergy tests revealed positive reactions to Japanese cedar pollen, but the non-seasonal clinical signs were not compatible with atopic dermatitis caused by this pollen. Results of hematological examination, serum chemistry and thyroid gland profile were normal. Examination of skin biopsy exhibited hyperplastic superficial perivascular dermatosis with severe acanthosis, excessive keratinocyte mitoses, patchy or diffuse mild spongiosis, and lymphocytic exocytosis in epidermis. Perivascular to interstitial mononuclear cells infiltration was seen in the superficial dermis. Based on the results of examination described above, epidermal dysplasia was diagnosed. Treatments with administration of antibiotics, etretinate, and prednisolone orally combined with topical ketoconazole cream and antiseborreic shampoos had no good results. Following treatment with long-term oral itraconazole at 10 mg/kg daily and chlorhexidine shampoos was successful. However, when itraconazole therapy was stopped, the condition worsened twice within 2 or 3 months. Readministration of itraconazole produced improvement within 4 weeks. This dog has now been controlled periodical itraconazole therapy.

• Bulletin of the Korean Chemical Society
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• v.27 no.2
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• pp.291-294
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• 2006

A highly sensitive high-performance liquid chromatographic-tandem mass spectrometric method (HPLC-MSMS) has been developed to quantify itraconazole in human plasma for the purpose of pharmacokinetic studies. Sample preparation was carried out by liquid-liquid extraction using loratadine as an internal standard. Chromatographic separation used a YMC $C_{18}$ column, giving an extremely fast total run time of 3 min. The method was validated and used for the bioequivalence study of itraconazole tablets in healthy male volunteers (n = 31). The lower limit of detection proved to be 0.2 ng /mL for itraconazole.

• Korean Journal of Clinical Pharmacy
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• v.33 no.2
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• pp.113-121
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• 2023

Background: Globally, the number of patients with aspergillosis is increasing, and the mortality rate remains high. This study aimed to investigate prescribing patterns of antifungal drugs for patients with aspergillosis in South Korea using real-world data. Methods: This retrospective cross-sectional study was performed using National Patient Sample (NPS) data collected by the Health Insurance Review and Assessment Service (HIRA) during 2011-2020. The use of antifungal drugs in patients with aspergillosis was investigated. Results:A total of 1374 patients were identified: 333 patients with invasive pulmonary aspergillosis (IPA) (24.2%), 436 patients with other PA (31.7%), 73 patients with other forms of aspergillosis (5.3%), and 532 patients with unspecified aspergillosis (38.7%). The odds of receiving an antifungal prescription were higher for IPA than for other PA (aOR, 0.233; p<0.001), and higher for hematologic malignancies than for respiratory disorders other than cancer or infections (aOR, 10.018; p<0.001). During each hospitalization period, 56.1% (97/173) and 6.4% (11/173) of IPA hospitalizations received voriconazole and itraconazole monotherapy, respectively, whereas 44.3% (27/61) and 27.9% (17/61) of other PA hospitalizations received itraconazole and voriconazole monotherapy, respectively. Among outpatients with IPA, 67.5% (85/126) and 26.2% (33/126) received voriconazole and itraconazole alone, respectively, whereas among outpatients with other PA, 86.1% (68/79) and 12.7% (10/79) received itraconazole and voriconazole alone, respectively, during the year. Conclusion: In Korea, voriconazole monotherapy was preferred in IPA inpatients, and itraconazole monotherapy was preferred in other PA inpatients. In the ambulatory care settings for IPA and other PA, itraconazole monotherapy was preferred.

• KSBB Journal
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• v.19 no.4
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• pp.321-326
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• 2004

Microparticles of an inclusion complex between itraconazole and 2-hydroxypropyl-${\beta}$-cyclodextrin (HP-${\beta}$-CD) were prepared using an environmentally-benign supercritical anti-solvent (SAS) process. In order to evaluate the degree of complexation, the thermal behavior of solid micro particulate complexes was investigated using differential scanning calorimetry. The experimental results obatined for the solubility and dissolution rate of the microparticulate inclusion complexes in a buffer solution of pH 1.2 showed that the complexation of itraconazole with HP-${\beta}$-CD results in a significant increase in the solubility and dissolution rate of itraconazole. For the microparticulate itraconazole/Hp-${\beta}$-CD inclusion complexes prepared by the SAS process, about 80% of itraconazole was found to dissolve in the buffer solution. Our experimental results confirmed that the SAS process is a promising method for the preparation of microparticles of water-insoluble drug/cyclodextrin inclusion complexes.

• Journal of Veterinary Clinics
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• v.22 no.2
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• pp.90-93
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• 2005

Itraconazole was found to be an effective antifungal for the treatment of canine Malassezia dermatitis (MD). MD was diagnosed in 18 dogs, which were treated with itraconazole administered orally at 5 mg/kg of body weight, q12hrs, for 21 to 30 days. High prevalence breeds of MD were Maltese $(22\%)$, Cocker Spaniel $(17\%)$, Pekingese $(11\%)$, and Vizsla $(11\%)$. The dermatological signs of Malassezia dermatitis were crust $(31\%)$, alopecia $(25\%)$, hyperpigmentation $(25\%)$, scales$(19\%)$, erythema $(13\%)$, lichenification $(11\%)$, pustule $(11\%)$, ear swelling$(11\%)$, papules $(5\%)$, and offensive odor $(5\%)$. Commonly affected areas were ear canal $(41\%)$, axillae $(18\%)$, groin $(15\%)$, perianal $(12\%)$, ventral aspect of the neck $(9\%)$, interdigital spaces$(1\%)$, and muzzle $(1\%)$. Sixty seven percent of dogs with MD had cocci. Clinical responses of itraconazole were seen good, moderate, no responses of itraconazole, in $89\%,\;0\%,\;and\;11\%$, respectively, according to the owner's satisfaction to follow up call. Recurrence was detected on five good responsive dogs and adverse effects of the treatment were detected in only one dog. On the basis of this clinical study, itraconazole is a good choice in the treatment of canine Malassezia dermatitis. Efficacy, frequency of administration and veterinary approval are the major advantages.

• Journal of Pharmaceutical Investigation
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• v.35 no.3
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• pp.165-171
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• 2005

Itraconazole is a triazole antifungal agent to inhibit most fungal pathogens. However, it is difficult for itraconazloe to be delivered by topical system due to its poor aqueous solubility. First, niosomes containing drug were prepared with span 60, cholesterol. tocopherol and poloxamer 407 as vesicle forming agents in an effort to increase solubility of itraconazole. And then prepared niosomes were dispersed in O/W creams (containing xanthan gum, glycerin, vaseline, glyceryl monostearate and $Cerix^{\circledR}-5$) or gels (containing xanthan gum and poloxamer 407). Both creams and gels were evaluated with respect to their rheological properties, in vitro permeation through excised skin of hairless mouse. Creams or gels containing niosome showed pseudoplastic flow and hysteresis loop. For both creams and gels, viscosity was increased with increasing the content of glycerine or vaseline and the content of gel forming polymer, respectively. In creams, the permeability of drug to skin was decreased with increasing the viscosity of cream. The permeability of drug was affected by pH as well as viscosity of gel. In vitro permeation test results demonstrated that cream formulations showed better permeability than gels. In conclusion, these results suggest that creams formulation containing niosome can be useful for the topical delivery of intraconazole.

• Microbiology and Biotechnology Letters
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• v.39 no.4
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• pp.387-389
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• 2011

A previous study of ours indicated that Citrus auranifoli oil possesses antifungal activity against Malassezia furfur and Malassezia pachydermatis. In this study, we evaluated the anti-M. furfur and M. pachydermatis activities of limonene, which is a major component of C. aurantifolia oil, using the disk diffusion method. We also examined cytotoxicity against human normal epithelial (Beas-2B) cells using the cytopathic effect reduction (CPE) method. The results revealed that the minimum fungicidal concentration (MFC) value of limonene is lower than the value for itraconazole. The MFC value of limonene was seen to be 7.81 ${\mu}g$/mL against M. furfur and 3.90 ${\mu}g$/mL against M. pachydermatis. MFC values of itraconazole against M. furfur and M. pachydermatis were 62.50 ${\mu}g$/mL and 31.25 ${\mu}g$/mL, respectively. In addition, it was noted that limonene was not toxic to Beas-2B cells with normal morphology at a concentration of 100 ${\mu}g$/mL. However, itraconazole exhibited weak toxicity at the same concentration. Therefore, our results indicate that limonene could potentially be effective at controlling M. furfur and M. pachydermatis infections with no cytotoxicity.

• Korean Journal of Veterinary Research
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• v.52 no.3
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• pp.163-167
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• 2012

Mosapride stimulated dietary motility was introduced because of the arrhythmogenic effect of cisapride. Cisapride, 5-HT receptor agonist, induces prolongation of QT interval. Additionally, this condition can raise the possibility of acute, "malignant" arrhythmias such as torsade de pointes. It is hard to find any reports about effects of mosapride on cardiac parameters in dogs. By confirming electrocardiogram (ECG) parameters, the surface extremity leads ECG that was obtained from the four-limb electrodes and which was recorded by an ECG recorder after administration of mosapride 3 mg/kg PO b.i.d, and mosapride 3 mg/kg with itraconazole 5 mg/kg PO b.i.d, respectively. QT interval was shortened on the days of 3, 5, and post-day 1 in both mosapride 3 mg/kg administrated group and mosapride with itraconazole group. Heart rate increased significantly. QTc was slightly prolonged in mosapride administration group and mosapride with itraconazole group. However, all dogs of QTc were in normal variation (150~250 msec). Besides, the dogs showed no side effects reported in human medicine during the administration with these drugs. Although mosapride can increase the heart rate, this study suggest that mosapride may be useful for the dogs with disorders of gastrointestinal motility because of no fatal arrhythmogenic effect inspite of administration with itraconazole in dogs.