Itraconazole

CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs--aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective. Although esthetically unpleasing to use so many drugs at once, the closely similar drugs of the original CUSP9 used together have been well-tolerated when given on a compassionate-use basis in the cases that have come to our attention so far. We expect similarly good tolerability for CUSP9*. The combined action of this suite of drugs blocks signaling at, or the activity of, AKT phosphorylation, aldehyde d...

Background: Itraconazole is a broad-spectrum antifungal agent that has been used to treat dermatomycosis and onychomycosis using continuous therapy. More recently the drug has been used as pulse dosing. Objective: Our purpose was to review the studies in which itraconazole pulse therapy (PT) has been administered in the management of dermatomycoses. Results: For tinea pedis and manuum, the recommended dosage is itraconazole 200 mg twice daily for 1 week (n = 220). A clinical response and mycologic cure rate of 90% ± 4% and 76% ± 6%, respectively, has been obtained. For tinea corporis/cruris, itraconazole 200 mg/day for 1 week (n = 354) resulted in a clinical response and mycologic cure rate of 90% ± 4% and 77% ± 6%, respectively. When three pulses of itraconazole are used to treat toenail onychomycosis (n = 1389), the clinical cure rate, clinical response, and mycologic cure rate at follow-up 12 months after the start of therapy were 58% ± 10%, 82% ± 3%, and 77% ± 5%, respectively. With two pulses for onychomycosis of the fingernails, the clinical cure rate, clinical response, and mycologic cure rate at follow-up, 9 months after the start of therapy, were 78% ± 10%, 89% ± 6%, and 87% ± 8%, respectively. Conclusion: Itraconazole PT is effective and safe in the treatment of tinea pedis/manuum, tinea corporis/cruris, and onychomycosis. (J Am Acad Dermatol 1997;37:969-74.)

To report successful treatment of ocular infection caused by the microsporidium Encephalitozoon cuniculi in a person with acquired immunodeficiency syndrome (AIDS) and nasal and paranasal sinus infection. Case report. Microsporidial infection in a person with AIDS and with chronic sinusitis and keratoconjunctivitis was diagnosed by Weber modified trichrome stain and transmission electron microscopy. Symptoms completely resolved with itraconazole treatment (200 mg/day for 8 weeks) after albendazole therapy (400 mg/day for 6 weeks) was unsuccessful. Itraconazole can be recommended in ocular, nasal, and paranasal sinus infection caused by E. cuniculi parasites when treatment with albendazole fails.

In this work, the cocrystallization approach was applied to itraconazole (ITR), a very slightly soluble triazole antifungal drug, which led to the formation of two new solid forms of ITR with 4-aminobenzoic acid (4AmBA) and 4-hydroxybenzamide (4OHBZA). A thermodynamic analysis of the solid-liquid binary phase diagrams for the (ITR + 4AmBA) and (ITR + 4OHBZA) systems provided conclusive evidence of the cocrystal stoichiometry: 1:1 for the cocrystal with 4-aminobenzoic acid, and 1:2 for the cocrystal with 4-hydroxybenzamide. Powder X-Ray diffraction analysis confirmed the formation of two different polymorphic forms of the [ITR + 4OHBZA] (1:2) cocrystal obtained either through solution or melt crystallization. Cocrystal formation and polymorphic transition processes were investigated in detail by the DSC and HSM methods. The thermodynamic functions of cocrystal formation were estimated from the solubility of the cocrystals and the corresponding solubility of the pure compounds at different temperatures. The combination of ITR and 4OHBZA was found to be more favorable than the reaction between ITR and 4AmBA in terms of both Gibbs energy and enthalpy. The pH-solubility behavior of the cocrystals was investigated at different pH values using eutectic concentrations of the components and the cocrystal solubility advantage was estimated. It was found that the cocrystallization of itraconazole with 4OHBZA and 4AmBA can potentially increase the drug solubility at pH1.2 and 37 • C by 225 and 64 times, respectively. The cocrystal dissolution behavior in biorelevant media was analyzed in terms of C max , σ max parameters (the maximum ITR concentration and supersaturation), and AUC (the concentration area under the curve during the dissolution-supersaturation-precipitation process). The cocrystals had similar σ max values during the dissolution and sustained supersaturation for up to 6 h, which gave them an advantage in the AUC values (13-37 times higher) over the drug. The differences in the dissolution profiles of the cocrystals were rationalized in terms of their dissolution rate values.

Itraconazole is an imidazole derivative and used for the treatment of local and systemic fungal infections. It is a BCS Class II drug having very low solubility in water i.e. 1-4ng/ml. T he oral use of Itraconazole is not much recommended as it has many side effects. The present research has been undertaken with the aim to develop a topical hydrogel formulation of Itraconazole loaded nanosponges to increase the solubility, permeability and stability of itraconazole. Itraconazole loaded nanosponge was prepared by emulsion solvent diffusion method by using different concentrations of ethyl cellulose as a polymer, Polyvinyl alcohol as surfactant and dichloromethane as cross linking agent. Physical characteristics of the nanosponges as well as the drug entrapment efficiency, percentage drug content, Percent yield, drug polymer compatibility, solubility studies of the nanosponges were investigated. Particle size analysis and surface morphology of nanosponges were performed. The scanning electron microscopy of nanosponges showed that they were spherical in shape and spongy in nature. Drug entrapment efficiency was found to be in the range of 42.75 % to 73.10 %. The optimized nanosponge formulation was loaded into hydrogel using carbopol 940 and studied for pH, viscosity, in vitro drug release. Of the nanosponge formulations prepared, F4 was found to show drug release of 70.62%. It was concluded that Itraconazole nanosponge hydrogel may have increased solubility, and drug release.

Summary. The authors report the clinical and microbiological findings of a 6-month follow-up of nine AIDS patients affected with cryptococcosis. Among these, seven patients suffered from meningoencephalitis and two from disseminated infection. The antifungal therapy during acute illness included the administration of amphotericin B at doses of 0.6 mg kg-1 day-1 i.v. plus flucytosine at doses of 100 mg kg-1 day-1 i.v. during the first 15 days followed by itraconazole at doses of 400 mg day-1 p.o. in the following 15 days. The maintenance treatment included itraconazole at doses of 200 mg day-1 p.o. indefinitely. During the 6-month follow-up, one patient died of hepatic failure related to C virus (HCV) hepatitis reactivation and another patient died of polymicrobial pneumonia. In two patients, the presence of multiple nodular lesions in the cerebral computerized tomography (CT) scan, related to cryptococcal granulomas, was associated with the persistance of fungi in the cerebrospinal fluid. In three patients with meningoencephalitis the three-drugs regimen was effective in eradicating the neurological infection, and relapses were not observed during the maintenance therapy with itraconazole during the 6-month follow-up. The two patients with haematogenous cryptococcosis did not relapse after the 6-month follow-up.Zusammenfassung. Die Studie informiert über einen 6-Monate-Zeitraum einer noch nicht abgeschlossenen klinisch-mikrobiologischen Beobachtung an neun Cryptococcose-AIDS-Patienten, sieben davon mit Cryptococcus-Meningoenzephalitis und zwei mit disseminierter Cryptococcose. Alle Patienten wurden in der akuten Phase mit Amphotericin B (0.6 mg kg-1 d-1 i.v.) und Flucytosin (100 mg kg-1 d-1 i.v.) 15 Tage lang behandelt. Anschließend erhielten die Patienten Itraconazol (400 mg d-1 per os) ebenfalls über 15 Tage. Als Dauernachbehandlung wurde Itraconazol (200 mg d-1) auf unbestimmte Zeit verabreicht. Während der 6-monatigen Beobachtungszeit starb ein Patient an Leberversagen aufgrund der Reaktivierung einer HCV-Hepatitis sowie ein weiterer an polymikrobieller Pneumonie. In zwei Fällen mit multiplen hypodensen Läsionen im Enzephalo-CT, interpretiert als granulomatöse Lokalisation der Cryptococcose, war die Prognose negativ, weil nach 30 Therapietagen die Liquorkultur noch positiv war. Bei drei Patienten erwies sich das Therapieregime als wirksam. Rückfalle wurden in der 6-monatigen Nachbeobachtungs-periode nicht beobachtet, ebenso wenig bei den beiden Patienten mit disseminierter Cryptococcose.