• Journal of Pharmaceutical Investigation
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• 제32권4호
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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.

• 한국임상약학회지
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• 제26권4호
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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.

• 한국임상수의학회지
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• 제21권2호
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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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• 제27권2호
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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.

• 한국임상약학회지
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• 제33권2호
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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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• 제19권4호
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• pp.321-326
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• 2004

본 연구에서는 초임계 이산화탄소를 이용한 SAS 공정을 난용성 약물인 이트라코나졸과 친수성 물질인 HP-$\beta$-CD의 포접복합체 미세입자의 제조에 적용하기 위한 기초 연구를 수행하였다. 이트라코나졸과 HP-$\beta$-CD를 1:2의 몰비로 혼합한 용액을 사용하여 35∼$65^{\circ}C$의 온도범위와 83∼140 bar의 압력범위에서 SAS 공정으로 이트라코나졸/HP-$\beta$-CD 포접복합체 미세입자를 제조하였으며, 이트라코나졸 및 HP-$\beta$-CD 원재료의 열적 특성과 비교함으로써 초임계 유체 공정에 의해 포접복합체를 제조할 수 있음을 확인하였다. 또한, SAS 공정에 의해 제조된 이트라코나졸/HP-$\beta$-CD 포접복합체의 인공위액에 대한 이트라코나졸의 용출시험을 수행한 결과 이트라코나졸 원재료와 이트라코나졸을 함유한 대표적 시판 제제인 스포라녹스 캡슐제와 비교해 투입된 이트라코나졸의 50∼80%에 해당하는 양이 용출개시 5분 만에 방출되는 매우 빠른 초기 용출특성을 보임을 확인할 수 있었다. 이트라코나졸 /HP-$\beta$-CD 포접복합체의 제조시 SAS 공정 조건이 35$^{\circ}C$에서 $65^{\circ}C$로 높아짐에 따라 이트라코나졸의 용출률이 감소하였을 뿐만 아니라 열분석 결과 이트라코나졸의 용융 피크의 세기도 점차로 증가하게 된다는 결과로부터 포접복합체의 형성이 이루어지는 주변 매질의 온도가 높아짐에 따라 초임계 이산화탄소 분자의 활동도가 증가하게 되어 이트라코나졸과 HP-$\beta$-CD의 포접복합체 형성에 필요한 결합력이 점차로 약해져서 포접 효율이 저하하게 됨을 확인할 수 있었다.

• 한국임상수의학회지
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• 제22권2호
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• pp.90-93
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• 2005

Malassezia 피부염으로 진단된 18두의 개를 대상으로 Itraconazole 5mg/kg을 1일 2회 경구 투여하여 치료효과를 알아보았다 치료반응을 보인 환자는 $88\%$이었으며 소양감과 피부병면은 치료후 1주일에 확연히 개선되었다. 치료대상견의 품종은 Haltese$(22\%)$, Cocker Sptuiel$(17\%)$, Pekingese$(11\%)$, Vizsla$(11\%)$이었다. 피부증상으로는 가피$(31\%)$, 탈모$(25\%)$, 색소침착$(25\%)$, 인설$(19\%)$, 발적$(13\%)$, 태선화$(11\%)$, 농포$(11\%)$ 귀부종$(11\%)$, 구진$(5\%)$의 순으로 냐타났다. 병변발생부위는 이도$(41\%)$, 액와부$(18\%)$, 서혜부$(15\%)$, 회음부$(12\%)$, 복측경부$(9\%)$, 지간부$(1\%)$, 총구부$(1\%)$ 이었다. 세포학적 검사시$61\%$의 환견에서 구균이 동시에 검출되었다. Itraconazole에 대한 임상반응은 $89\%$가 치료반응을 보였고 (2두)$11\%$는 치료반응을 보이지 않았다 치료반응을 보인 환자 중 5두는 재발되었고 1두는 갑상선 기능저하증이었으며 나머지 4두는 재발의 원인을 확인할 수 없었다. 1두에서 투여 후 28일에 식욕결집, 침울의 증상이 발현되어 투약을 중지하였다. 따라서itraconazole을 5mg/kg을 1일 2회 경구투여는 Malassezia 피부염에 효과적인 치료로 사료된다

• Journal of Pharmaceutical Investigation
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• 제35권3호
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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.

• 한국미생물·생명공학회지
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• 제39권4호
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• pp.387-389
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• 2011

우리의 이전의 연구에서 Citrus auranifoli 오일은 Malassezia furfur와 Malassezia pachydermatis에 대해 항곰팡이 활성을 나타낸다는 것을 보여주었다. 본 연구에서 Citrus auranifoli 오일의 주요 성분인 리모넨(limonene)의 M. furfur와 M. pachydermatis에 대한 저해효과를 디크스 확산 방법(disk diffusion method)에 의해 측정하였고, Beas-2B 세포에 대한 세포독성을 cytopathic effect reduction 방법에 의해 측정하였다. Limonene의 최소곰팡이저해농도(minimum fungicidal concentration)는 양성대조구인 itraconazole보다 더 낮았고, 100 ${\mu}g$/mL의 농도에서 Beas-2B cells에 대한 세포독성을 나타내지 않았다. 그러나 itraconazole은 같은 농도에서 약한 세포독성을 나타내었다. 그러므로, 우리의 결과에서 limonene는 비세포독성과 함께 M. furfur and M. pachydermatis의 성장저해를 하는데 효과적이라는 것을 보여준다.

• 대한수의학회지
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• 제52권3호
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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.