Oral Administration Of Itraconazole Research Articles

Topical hydrophilic gel with itraconazole-loaded polymeric nanomicelles improves wound healing in the treatment of feline sporotrichosis

Sporotrichosis is a superficial fungal disease that can affect animals and humans. The high number of infected cats has been associated with zoonotic transmission and contributed to sporotrichosis being considered by the World Health Organization as one of the main neglected tropical fungal diseases for 2021–2030. Oral administration of itraconazole (ITZ) is the first choice for treatment, but it is expensive, time-consuming, and often related to serious adverse effects. As a strategy to optimize the treatment, we proposed the development of a hydrophilic gel with nanomicelles loaded with ITZ (HGN-ITZ). The HGN-ITZ was developed using an I-optimal design and characterized for particle size, Zeta potential, drug content, microscopic aspects, viscosity, spreadability, in vitro drug release, in vitro antifungal activity, and clinical evaluation in cats. The HGN-ITZ showed a high content of ITZ (97.3 ± 2.1 mg/g); and characteristics suitable for topical application (viscosity, spreadability, globules size, Zeta potential, controlled drug release). In a pilot clinical study, cats with disseminated sporotrichosis were treated with oral ITZ or HGN-ITZ + oral ITZ. A mortality rate of 21.3% was observed for the oral ITZ group compared to 5.3% for the HGN-ITZ + oral ITZ group. In a cat with a single lesion, topical treatment alone (HGN-ITZ) provided complete healing of the lesion in 45 days. No signs of topical irritation were observed during the treatments, suggesting that HGN-ITZ can be a promising strategy in the treatment of sporotrichosis.

Eumycetoma Caused by Madurella pseudomycetomatis in a Captive Tiger (Panthera tigris).

A captive-kept adult male tiger presented with a large cutaneous and subcutaneous mass on the thigh with a fistula. During sedation, multiple nodules were detected and samples for a histopathological exam were collected. Histologically, granulomatous panniculitis and dermatitis were seen around dense aggregates of pigmented fungal hyphae, and a diagnosis of phaeohyphomycosis was made; considering the clinical features, it was classified as a eumycotic mycetoma. This is a rarely reported subcutaneous fungal infection in humans and animals, caused by dematiaceous fungi. Clinically, it is characterized by tumefaction, fistulous sinus tracts, and the formation of macroscopically visible grains. In the literature, only a few infections in wild felids have been reported. In this case, Fontana-Masson staining better showed pigmentation and panfungal PCR and sequencing identified Madurella pseudomyectomatis (OP623507) as the causative agent. Systemic therapy with oral administration of itraconazole was planned, but the patient died during the first period of treatment. The animal was not submitted for post-mortem examination. Visceral dissemination of the agent cannot be excluded. To the authors' knowledge, this is the first report of eumycotic mycetoma by Madurella pseudomycetomatis in a captive tiger.

Evaluation of the air sac volume of penguins with respiratory diseases using computed tomography.

Captive penguins with respiratory diseases exhibit advanced pathological conditions upon the appearance of clinical signs. Therefore, the successful treatment of respiratory diseases remains difficult after the onset of clinical signs, leading to high mortality rates. In this study, we measured air sac volume using computed tomography (CT) to evaluate the respiratory condition of penguins. In a regular quarterly health checkup, blood samples were collected from 45 penguins housed at an aquarium in Hokkaido, Japan. A total of 12 penguins with abnormal blood parameters underwent CT. The air sac volumes were calculated in three-dimensional CT, and the scatter plots of the air sac volumes and body weights were analyzed. No correlation was found between the air sac volume and body weight in both the gentoo and king penguins. Two gentoo penguins with infiltration and one king penguin with multiple nodules on CT were tentatively diagnosed with aspergillosis and treated with oral administration of itraconazole. Follow-up CT examination was performed until the outcome: healed or died. The mean air sac volumes of the two gentoo penguins, which recovered after treatment, increased from 273.9 and 329.0 cm3 before healing to 449.0 and 424.6 cm3 after healing, respectively. Meanwhile, the air sac volume of the king penguin, which subsequently died, decreased from 1,556.9 to 920.6 cm3 despite treatment. Changes of the air sac volume in the same individual could be useful for evaluating the respiratory condition of penguins.

Chimeric antigen receptor T cells targeting CD7 in a child with high-risk T-cell acute lymphoblastic leukemia

Effective systemic treatments for relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) are limited. Recent clinical application of chimeric antigen receptor (CAR) immunotherapy has demonstrated successful control of B-cell malignancies by CAR-T cells; however, designing CARs for T-ALL remains a challenge. CD7 overexpression in T-cell malignancies may be an attractive target for immunotherapy in T-ALL. This study aimed to describe the safe and effective use of autologous CD7-CAR T cells (4SCAR7) for the treatment of T-ALL with induction failure in an 11-year-old patient. Based on The Chinese Children’s Cancer Group-ALL (CCCG-ALL) study protocol, minimal residual disease (MRD) by flow cytometry (FC) analysis was detected on days 19 and 46 of remission induction. At the end of remission-induction chemotherapy, the patient achieved morphologic complete remission, though with MRD 16.13% and RT-PCR of KMT2A-MLLT1 fusion positive, which indicated induction failure. The cerebrospinal fluid (CSF) was negative for blasts at diagnosed. CAR-T therapy and allogeneic transplant were recommended as the next treatment options. CD3+ lymphocytes were collected from the patient 18 days after the high-dose MTX chemotherapy through leukapheresis. The 4SCAR7 CD7-targeting CAR-T cells were generated thereafter. The patient received lymphodepleting chemotherapy prior to 4SCAR7 infusion. Oral administration of itraconazole and sulfamethoxazole was performed from day 0 after CAR-T cell infusion. The patient did not have hypotension, hypoxia, or serious biochemical change or abnormality, but had fever on day 9. Although grade 1 cytokine-release syndrome (CRS) was diagnosed, it was successfully treated with ibuprofen. Anti-CD7 CAR transgene copy numbers in peripheral blood were determined by qPCR, which showed effective expansion initially, then dropped quickly, and persisted at a low level. Although experienced cytopenia from days 14 to 21, the patient achieved remission on day 17. After complete remission, the patient received hematopoietic stem cell transplantation (HSCT) and has recovered well to thisdate. Overall, this report suggested that 4SCAR7 could be a safe and effective strategy for the treatment of pediatric patients with high-risk T-cell malignancies.

Koncentracije itrakonazola i hidroksi-itrakonazola nakon oralne primene leka kod zdravih ljudi - uticaj pola

Introduction: Itraconazole is an antifungal drug belonging to the triazole group. After oral application, it is rapidly absorbed, but its bioavailability is reduced due to an intensive first-pass through the liver metabolism effect. A large number of metabolites (the most important of which is hydroxyitraconazole) are produced by isoform CYP3A4 of cytochrome P450. The variability of itraconazole pharmacokinetics is the result of numerous factors that have not yet been fully clarified. Our study aimed to investigate the influence of gender on itraconazole and hydroxyitraconazole plasma concentrations in healthy adults after an oral application of a single dose of itraconazole. Methods: Pharmacokinetic analysis was performed after oral administration of itraconazole in a single dose of 100 mg to 22 male and 16 female healthy volunteers. Blood samples were collected before taking the drug and at appropriate time intervals up to 72 hours later. Itraconazole and hydroxyitraconazole concentrations were determined using a validated liquid chromatography method with mass spectrometric detection (LC-MS/MS) and their pharmacokinetic parameters were calculated by using the Kinetica programme, version 5.0: Cmax, Tmax, PIK (0-72), PIK (0-∞), T1/2, and Ke. Results: The median values of both itraconazole and hydroxyitraconazole were lower in women in comparison to men during the whole period of observation. Moreover, median values of Cmax, PIK(0-72) and PIK(0-∞) parameters were also significantly lower in women, concerning both itraconazole (p=0.005, 0.036 and 0.036, respectively) and its metabolite (p=0.004, 0.010 and 0.044, respectively). Elimination parameters - T1/2 and Ke did not differ between genders. Conclusion: Women were less exposed to itraconazole and its active metabolite than men following an oral application of the drug, possibly as a result of lower bioavailability due to a more intense pre-systemic metabolism, as a result of a higher expression and/or activity of the isoform enzyme, which metabolises itraconazole, and which would need to be confirmed by pharmacogenomic analysis.

Characteristic imaging findings of the respiratory system in penguins with suspected aspergillosis in an aquarium.

Twenty penguins, including the King penguin (Aptenodytes patagonicus), Gentoo penguin (Pygoscelis papua), and African penguin (Spheniscus demersus), housed at an aquarium in Hokkaido, Japan, underwent regular health screening via blood test, and five penguins with suspected aspergillosis were extracted. In cases 1 and 2, a thickened membrane and/or fluid level and/or calcification in the air sac were observed on both radiography and computed tomography (CT). These two penguins died after 19 and 43 days, respectively. At the time the radiographic changes were observed, the disease had likely progressed to a point at which it was too late for recovery. Aspergillus fumigatus infection was confirmed by nucleotide sequence analysis in case 1. In case 3, infiltration in the pulmonary parenchyma was observed on CT, and the infiltration disappeared following oral administration of itraconazole as diagnostic therapy for 8 months. In case 4, defects in the pulmonary parenchyma were observed only on CT. These defects remained unchanged in size for 7 months despite the lack of any treatment, and were not considered clinically significant. However, the blood antigen level in case 5 was increased, both radiography and CT were unremarkable. The combination of a screening blood test and CT examination could be useful clues for an early diagnosis of aspergillosis as well as for initiating treatment.

Associação de itraconazol e iodeto de potássio no tratamento da esporotricose disseminada em um felino em Palotina, PR – relato de caso

Sporotrichosis is a zoonosis caused by a fungus of the Sporothrix gender, and transmitted through open wounds. Because of their closed territorial nature, intact male cats are most frequently affected. We describe the treatment of an adult, rescued intact male cat presented with disseminated ulcerative skin lesions affecting face, ears, neck, thoracic limb, and scapular region. Cytology of the lesions revealed the presence of macrophages containing a large number of oval oblong yeast structures consistent with Sporothrix sp. The cat was treated with once a day oral administration of itraconazole (100mg/cat) and potassium iodide (5mg/kg). Full remission was observed 126 days after beginning of treatment.

Real-Time PCR Detection of the Basidiomycetous Fungus Bjerkandera adusta: A Tool to Identify Itraconazole Responder Patients with Unexplained Chronic Cough

Background: Filamentous basidiomycetes (f-BMs) are involved in some unexplained chronic cough (UCC) cases that can be improved by the administration of antifungal agents. The disease concept was termed fungus-associated chronic cough (FACC). The current diagnostic criteria warrant environmental fungi isolation from respiratory specimens, which is hardly conceivable for such fungi. Objectives: This study aimed to detect the f-BMs Bjerkandera adusta, the most common pathogen in FACC, from respiratory specimens of patients with UCC using real-time polymerase chain reaction (PCR). It also evaluated the applicability of the PCR system to detect antifungal agent responders among patients with unexplained cough. Methods: The PCR system specific to B. adusta was developed and its utility was evaluated using sputum samples from 23 patients with chronic cough. Results: B. adusta was detected in 10 out of 14 patients with UCC (71.4%), in contrast to only 2 out of 9 patients with non-UCC (22.2%; p < 0.05 with the Fisher’s exact test). The copy number of the samples correlated with the therapeutic impact score for cough symptoms following the oral administration of itraconazole. Conclusion: Development of the real-time PCR system enabled us to demonstrate that many patients with UCC might be influenced by B. adusta, a fact evidenced by the improvement of symptoms with itraconazole administration in most PCR-positive patients. This method would help in detecting itraconazole responders among patients with UCC when the isolation of f-BMs is not achievable.

Esporotricose óssea em gato causada por Sporothrix brasiliensis

Background: Sporotrichosis is a deep cutaneous mycosis caused by the Sporothrix species complex, dimorphic fungi of which at least five are of clinical importance: S. brasiliensis, S. globosa, S. luriei, S. mexicana, and S. schenckii sensu stricto. The disease affects humans and animals, especially cats, which can manifest a wide spectrum of clinical sings, from cutaneous-lymphatic involvement to disseminated form. Infection usually results from direct inoculation of the fungus into skin. Zoonotic transmission is associated with scratching or biting of sick cats. The aim of this work was to report an atypical case of bone sporotrichosis in a cat.Case: A 5-year-old, male, neutered, mongrel and indoor cat was present at the Veterinary Clinic Hospital, Federal University of Rio Grande do Sul (HCV-UFRGS), Porto Alegre, Brazil, with lameness and increased volume in the left hindlimb. The animal had been treated intermittently with itraconazole during the last three years due to another cutaneous lesion which was recurrent and undiagnosed. A firm and painful mass was found in tarsal region of left hindlimb, that had approximately 5 cm in diameter. Radiographic examination of the left tibial-tarsal joint revealed bone lysis in the fifth metatarsal calcaneus, in addition to periosteum proliferation in calcaneus, tibio-tarsal subluxation, presence of osteophytes in tarsal bones and increase in soft tissue volume. Histopathological analysis of the biopsied tissue showed piogranulomatous inflammation. No yeast-like structures were observed in cytopathological exam. Tissue fragments were plated and Sporothrix sp. complex growth in mycological culture (Sabouraud Cycloheximide Chloramphenicol Agar). Physiological tests (growth rate at different temperatures and assimilation of sucrose and raffinose) were conducted for the differentiation of the species of complex. Molecular identification was performed using panfungal primers (ITS3-F / ITS4-R). The diagnosis of bone sporotrichosis caused by Sporothrix brasiliensis was based on clinical signs, mycological (confirmed by isolation and identification in culture medium) and molecular methods. Treatment was based on excision of the limb associated with oral administration of itraconazole and silymarin for two months. Unfortunately, three months later new nodules were seen at the abdomen and biopsy samples were positive in a new fungal culture for Sporothrix sp. Oral treatment was then restarted for four months. The cat is now free of lesions for six months and clinical monitoring visit is usually done once per month.Discussion: Sporotrichosis is a fungal infection with worldwide distribution, mostly in tropical and subtropical countries, characterized by cutaneous and subcutaneous lesions with regional lymphocutaneous dissemination, but some pulmonary and systemic infections in human have been reported. Cats are frequently infected with sporotrichosis in Brazil and develop a scattered cutaneous condition. On the other hand, the systemic form of the disease have been more observed with a disseminated respiratory or systemic condition, including infection of the lungs, liver, spleen, kidney, testis, eyes, bones, central nervous system, gastrointestinal tract, and mammary glands may also be affected. The occurrence of bone sporotrichosis, without skin lesions, show the high susceptibility of these animals to infection by Sporothrix. Molecular methods for the differentiation of Sporothrix complex are needed when the conventional methodology (histopathology and culture) does not allow the identification of the agent. The reference standard for diagnosing sporotrichosis is microscopic characterization of the pathogen isolated in culture. In our study, although the culture was positive, PCR was necessary for detecting and identifying Sporothrix brasiliensis. The reported case of bone sporotrichosis emphasizes the importance of a conclusive and differential diagnosis in feline lytic bone lesions based on the detection of fungal in the tissue by molecular methods associated with the isolation of the agent in a fungal culture.

Etiologic significance of &lt;i&gt;Aspergillus terreus&lt;/i&gt; in primary cutaneous mycosis of an agricultural worker

This pilot study was aimed to elucidate the growing role of non-dermatophytic filamentous moulds in the cutaneous lesions of laborers who worked in agriculture field in the villages of Bharauch, Gujarat ,India. Eighteen patients (13 males and 5 females, aged 21 to 46 years) with various skin problems presented to the outpatient department (OPD) of Welfare Hospital and Research Center, and Shashwat Skin Clinic, Bharauch, India were examined for the non-dermatophytic filamentous fungi by using standard mycological techniques. All the specimens were treated in 10 % potassium hydroxide solution of direct microscopy; and cultural isolation was done onto Sabouraud medium with chloramphenicol. The detailed identification of fungal isolates was carried out in “ Narayan” stain. The treatment of patient was attempted with oral administration of itraconazole. Aspergillus terreus was identified in the cutaneous lesion of 1 of the 18 patients both by direct microscopy as well as by cultural isolation. The cinnamon-brown coloured colonies of A. terreus grew in pure culture from the biopsied tissue on Sabouraud dextrose agar with chloramphenicol. In “Narayan” stain, conidial heads of A. terreus were found compact, biseriate, and densely columnar. The patient had received trauma on the skin of right lower leg by wooden splinter while working in the field. The oral administration of itraconazole for 12 weeks showed good clinical response. The demonstration of A. terreus in the skin lesion by direct microscopy and cultural isolation, and good response to antifungal drugs clearly indicated that our patient was suffering with cutaneous mycosis. The patient with chronic cutaneous lesion, history of the skin trauma, and occupational exposure to the soil should be investigated for cutaneous mycosis. The immediate attention to traumatic injury to the skin is highly imperative to prevent the further complications. This seems to be first report of primary cutaneous mycosis due to A. terreus in an immunocompetent patient from this part of India.

Effect of Triazole Antifungal Agents on the Drug Secretion Process in Rat Small Intestine: Contribution of P‐glycoprotein

The effect of triazole antifungal agents on the drug secretion process from the serosal to the mucosal side in small intestine was studied using rat everted intestinal sacs. Rhodamine 123 was used as a model drug mediated by P-glycoprotein. The effect of inhibitors, verapamil and triazole antifungal agents was investigated by measuring the efflux of rhodamine 123. Efflux was significantly reduced by the addition of verapamil. Fluconazole had no effect on the efflux of rhodamine 123, while the efflux of rhodamine 123 was significantly reduced by oral administration of itraconazole. These results suggest that inhibition of drug secretion by P-glycoprotein in intestine may be involved in the interaction between various drugs and itraconazole.

Summarization of Tinea Capitis Cases Encountered at a Clinic in the Past 5 Years

Twelve cases of tinea capitis were encountered at a clinic in Kumamoto prefecture between April 2004 and December 2008. Patients were boys aged between 2 and 18 in 11 cases, and a woman aged 50 years in 1 case. The pathogen was Microsporum canis in 6 cases, and Trichophyton tonsurans in 6 cases. In the cases with M. canis , patients were boys aged 2 to 8 years in 5 cases, and the type of disease was non-inflammatory in 5 cases and inflammatory in 1 case. The patients with T. tonsurans were boys aged 12 to 18 years (judo athletes in 5 cases) and the type of disease was inflammatory in 2 cases and black dot in 4 cases. Three of the M. canis cases were treated with oral administration of itraconazole (ITCZ) at doses of 2.4-4.0 mg/kg/day, and the other 3 with terbinafine hydrochloride (TBF) at doses of 2.6-4.6 mg/kg/day. The duration of treatment was 8-14 weeks with ITCZ, and 4-8 weeks with TBF. In the T. tonsurans cases, TBF was orally administered at doses of 1.4-2.4 mg/kg/day for a period of 8-12 weeks. In one case of non-inflammatory M. canis infection (Case 6) and one case of inflammatory T. tonsurans infection (Case 10), treatment was initiated with the dose recommended in Japan, but symptoms did not improve; therefore the dose was doubled according to European and American guidelines and the patients recovered. As tinea capitis frequently resists treatment, establishment of treatment guidelines is necessary.

Pharmacokinetics of itraconazole after intravenous and oral dosing of itraconazole‐cyclodextrin formulations

The current research evaluated and compared the efficacy of hydroxybutenyl-beta-cyclodextrin (HBenBCD) and hydroxypropyl-beta-cyclodextrin (HPBCD) as enhancers of itraconazole solubility and oral bioavailability. At 10 wt% cyclodextrin, 17-fold and 3.8-fold increases in itraconazole aqueous solubility were observed in the presence of HBenBCD and HPBCD, respectively. Significant differences in the dissolution of itraconazole in the presence of these two cyclodextrins were also observed. Itraconazole pharmacokinetics is known to exhibit a significant food effect. However, testing in biorelevant media indicated that no food effects should be observed after oral administration of itraconazole:HBenBCD complexes. Formulations of itraconazole with HBenBCD were prepared and these complexes, along with the commercial forms of itraconazole with and without HPBCD (Sporanox) were administered to male Sprague-Dawley rats by oral and intravenous routes. Intravenous administration of itraconazole formulated with HBenBCD resulted in a higher AUC relative to Sporanox. When administered as oral solutions, the itraconazole:HBenBCD formulation provided higher oral bioavailability than the Sporanox oral solution. When administered as solid formulations, the itraconazole:HBenBCD solid formulation provided a 2x increase in oral bioavailability relative to the Sporanox solid formulation. No food effects were observed with the itraconazole:HBenBCD solid dosage forms. Drug/metabolite ratios were dependent upon the dosage form.

Reduction in the growth of non‐dermatophyte moulds by itraconazole: evaluation by corneofungimetry assay: Beeinträchtigung des Wachstums von Nicht‐Dermatophyten‐Schimmeln durch Itraconazol: Bewertung mittels korneofungimetrischer Methode

The activity of itraconazole against fungi of dermatological importance was studied using corneofungimetry performed on four test organisms: Aspergillus flavus, Fusarium oxysporum, Scopulariopsis brevicaulis and Scytalidium dimidiatum. The human stratum corneum used in the bioassay was harvested from healthy volunteers and from patients undergoing treatment with itraconazole 200 mg daily for at least 2 weeks. A fungal mycelium grew on all untreated stratum corneum samples within 1 week. The pattern and extent of growth varied greatly among the test organisms. An inhibitory effect was observed on the itraconazole-treated samples. However, the level of inhibition was higher than that expected by calculating itraconazole minimum inhibitory concentrations in a reference susceptibility test. It is concluded that some non-dermatophyte moulds of medical importance can grow by forming hyphae on human stratum corneum. However, the process is partly inhibited by some unknown mechanisms originating from the stratum corneum itself. It is further inhibited by the oral administration of itraconazole. This global effect might be the result of the complementation inhibition due to the drug and/or some unknown components of the stratum corneum.

Prophylaxis of Candida and Aspergillus infections with oral administration of itraconazole.

The broad-spectrum oral triazole antifungal, itraconazole, has been shown to be effective in the treatment of superficial and systemic infections with fungi including Candida albicans, C. krusei and C. glabrata, Cryptococcus, Aspergillus, Histoplasma, Blastomyces and others. Its broad spectrum of activity, high and persistent tissue levels and favourable safety profile suggest that it may be appropriate for the prevention of opportunistic fungal infections in at-risk patients. In this study, itraconazole's prophylactic efficacy was tested against experimental models of Candida and Aspergillus infection. A single dose of 1.25 mg kg-1 or 2.5 mg kg-1, given 1 h before vaginal infection with C. albicans, protected 50% of treated rats. In systemic and disseminated candidosis, prophylaxis with itraconazole reduced both folliculitis and organ Candida content in guinea pigs. Amphotericin B was also used in this study and was found to be less efficacious than itraconazole. Itraconazole prolonged survival when administered to guinea pigs before experimental induction of systemic and invasive aspergillosis. In all cases, increasing the itraconazole dosage increased its prophylactic efficacy. Therefore, as the clinical efficacy of itraconazole is accurately reflected by the results of animal models, this study shows itraconazole to be a potential prophylactic therapy for patients at risk of opportunistic fungal infection.

Treatment of Deep-Seated Candidosis with Itraconazole: Multicentre Study in Japan

A multicentre clinical trial of itraconazole for deep-seated mycoses was carried out in 25 hospitals in Japan. The clinical efficacy and safety of itraconazole administered to 31 patients with candidosis are reported here. The diagnosis was confirmed by microscopy, culture, histology, serology, biopsy, radiology and/or endoscopy. Of the patients, 7 had candidaemia, 4 had pulmonary candidosis, 13 had oesophageal candidosis and 7 had urinary tract candidosis. The mean age of the patients was 57.8 years (range, 18-87 years). They had underlying diseases, such as haematological malignancy, acquired immune deficiency syndrome (AIDS) and cancer, leading to immunocompromise. The patients received itraconazole, 50-200 mg/day for 4-60 days (mean, 18.8 days). The overall clinical efficacy of itraconazole was 90% (27/30); in candidaemia it was 83.3% effective (5/6); in pulmonary candidosis, 100% (4/4); in oesophageal candidosis, 84.6% (11 /13); and in urinary tract candidosis, 100% (7/7). Eradication <i>of Candida </i>spp. was observed in 24 of the 31 patients. Itraconazole was well tolerated; eosinophilia and elevation of serum alanine aminotransferase and &#915;-glutamyl transferase were each observed in 1 patient. Determination of the serum levels of itraconazole confirmed that effective concentrations were reached. In conclusion, oral administration of itraconazole once or twice a day was well tolerated by all the patients, and satisfactory responses were obtained.

Itraconazole in the treatment of superficial mycoses-a double-blind study vs. placebo

Ninety-four patients with dermatophytosis and 16 patients with pityriasis versicolor were assigned under double-blind conditions to oral itraconazole (100 mg once daily) or placebo. The medication consisted of two capsules, each containing 50 mg of active substance, or placebo and was given for 15 or 30 days in patients with dermatophytosis and for 15 days in patients with pityriasis versicolor. Patients with pityriasis versicolor who had not responded at the end of the double-blind period were treated on an open basis with itraconazole (100 mg once daily) for 15 days. In the treatment of dermatophyte infections for 30 days, both clinical response and mycological cure were significantly superior in the itraconazole group compared with placebo. Oral administration of itraconazole (100 mg once daily) was also highly efficacious in the treatment of pityriasis versicolor. None of the placebo patients was clinically or mycologically cured at the end of the double-blind phase compared to seven out of eight itraconazole patients. All placebo patients who entered the open phase responded to itraconazole treatment. Three itraconazole-treated patients and nine placebo-treated patients reported side-effects.