Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new itraconazole research articles will be listed here shortly after becoming available to us.
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Medical research on itraconazole
Eur J Clin Pharmacol. 2008 Jun 27;
Cordoba R, Ramirez E, Lei SH, Lopez de la Guia A, Sanjurjo MJ, Carcas AJ, Hernandez-Navarro F
Eur J Pharm Biopharm. 2008 Jun 6;
Janssens S, Humbeeck JV, Mooter GV
In order to improve the in vitro performance and stability of co-spray-dried itraconazole/Inutec SP1 systems, the influence of adding PVPVA 64, a polymer that is compatible with itraconazole, was evaluated. Dissolution tests were carried out on several itraconazole/PVPVA 64/Inutec SP1 compositions and spray-dried itraconazole/PVPVA 64 powders were used as references. The physicochemical properties of the samples were assessed with modulated temperature differential scanning calorimetry (MDSC), X-ray powder diffraction (XRD) and environmental scanning electron microscopy (ESEM). Physicochemical analysis revealed that there is no interaction between itraconazole and Inutec SP1 and that sufficient amount of PVPVA 64 is required to keep the drug molecularly dispersed. The improvement of the ternary solid dispersions over the binary solid dispersions was composition dependent. On one hand the increased drug/PVPVA 64 ratio in the ternary systems slowed dissolution down, on the other hand this was compensated by the solubilizing power of Inutec SP1.
Central nervous system histoplasmosis.
Curr Treat Options Neurol. 2008 May; 10(3): 161-7
Saccente M
Involvement of the central nervous system (CNS) is recognized clinically in 5% to 10% of patients with progressive disseminated histoplasmosis. The risk of developing CNS histoplasmosis is increased in individuals with impaired cellular immunity, but not all patients with this condition are immunocompromised. Clinical syndromes include chronic meningitis, focal parenchymal lesions of the brain or spinal cord, stroke due to infected emboli, and diffuse encephalitis. CNS histoplasmosis should be considered in any patient with one of these syndromes who has resided in an area endemic for histoplasmosis. A high index of suspicion is necessary when extraneural signs and symptoms are absent. Culture of the causative fungus, Histoplasma capsulatum, from cerebrospinal fluid, brain tissue, or other sites is the gold standard for diagnosis. In culture-negative cases, detection of H. capsulatum antigen in cerebrospinal fluid, urine, or blood is helpful diagnostically. Aggressive and prolonged antifungal therapy is indicated in all cases of CNS histoplasmosis. There are no data from prospective comparative trials upon which to base specific recommendations for treatment. Expert opinion favors an initial course of liposomal amphotericin B, followed by at least 1 year of itraconazole.
Acute blastomycosis thyroiditis.
Thyroid. 2008 Jun; 18(6): 659-61
Moinuddin S, Barazi H, Moinuddin M
Acute thyroiditis is very unusual, and fungal thyroiditis is even more rare. Cervical blastomycosis, on one occasion masquerading as a thyroid mass, has been reported. Here we report the first case of acute blastomycosis infection of the thyroid documented by biopsy and imaging studies. The patient was a 23-year-old woodcutter with no history or features of overt immunodeficiency. The initial response to Itraconazole therapy was satisfactory.
J Med Assoc Thai. 2008 Mar; 91(3): 309-15
Isipradit S
OBJECTIVE: To assess the efficacy of 2% fluconazole subconjunctival injection as an adjunctive treatment in severe recalcitrant fungal corneal ulcer. DESIGN: Retrospective, non-comparative interventional case series. MATERIAL AND METHOD: From January 2007 to August 2007, the present study included six eyes of six patients with severe fungal corneal ulcer that did not respond to therapy with topical antifungal drugs, oral itraconazole (200 mg) twice a day and 10 microg intracameral amphotericin B. All of them were treated with 0.5 ml of 2% fluconazole subconjunctival injection twice a day as adjunctive therapy for 5 days then once a day till 14 days RESULTS: Three patients were successfully treated within 14 days. Two patients partially responded, and one of them underwent evisceration. The last patient did not respond to treatment and enucleation was done. Severe local and systemic side effects were not found. CONCLUSION: 0.5 ml of 2% Fluconazole subconjunctival injection can be a very useful treatment as adjunctive therapy for severe fungal keratitis, with a few mild complications, especially in cases of impending perforation or post operative such as glue application for ruptured cornea.
Clin Pharmacokinet. 2008; 47(7): 463-74
Neuvonen PJ, Backman JT, Niemi M
HMG-CoA reductase inhibitors (statins) dose-dependently lower both the level of low-density lipoprotein cholesterol and risk of cardiovascular disease. In 2004, the UK approved a low-dose over-the-counter (OTC) simvastatin, but the US has rejected applications for non-prescription preparations of statins. The pharmacokinetics and interaction potentials of the possible OTC candidate statins simvastatin, lovastatin, fluvastatin and pravastatin are clearly different. Simvastatin and lovastatin are mainly metabolized by cytochrome P450 (CYP) 3A, fluvastatin is metabolized by CYP2C9, and pravastatin is excreted largely unchanged. Several cell membrane transporters can influence the disposition of statins, e.g. the organic anion transporting polypeptide (OATP) 1B1 enhances their hepatic uptake. The c.521T>C (p.Val174Ala) genetic polymorphism of SLCO1B1 (encoding OATP1B1) considerably increases the plasma concentrations of simvastatin acid and moderately increases those of pravastatin but seems to have no significant effect on fluvastatin. Strong inhibitors of CYP3A (itraconazole, ritonavir) greatly (up to 20-fold) increase plasma concentrations of simvastatin, lovastatin and their active acid forms, thus enhancing the risk of myotoxicity. Weak or moderately potent CYP3A inhibitors such as verapamil, diltiazem and grapefruit juice can be used cautiously with low doses of simvastatin or lovastatin, but their concomitant use needs medical supervision. Potent inducers of CYP3A can greatly decrease plasma concentrations of simvastatin and simvastatin acid, and probably those of lovastatin and lovastatin acid. Although fluvastatin is metabolized by CYP2C9, its concentrations are changed less than 2-fold by inhibitors or inducers of CYP2C9. Pravastatin plasma concentrations are not significantly affected by any CYP inhibition and only slightly affected by inducers. Ciclosporin inhibits CYP3A, P-glycoprotein and OATP1B1. Gemfibrozil and its glucuronide inhibit CYP2C8 and OATP1B1. Ciclosporin and gemfibrozil increase plasma concentrations of statins and the risk of their myotoxicity, but fluvastatin seems to carry a smaller risk than other statins. Inhibitors of OATP1B1 may decrease the benefit-risk ratio of simvastatin, lovastatin and pravastatin by interfering with their (active acid forms) entry into hepatocytes. Understanding the differences in the pharmacokinetics and interaction potential of various statins helps in their selection for possible non-prescription status. On the pharmacokinetic basis, fluvastatin and pravastatin can be better choices than simvastatin or lovastatin for an OTC statin.
J Clin Microbiol. 2008 Jun 18;
Pfaller MA, Messer SA, Boyken L, Rice C, Tendolkar S, Hollis RJ, Diekema DJ
Few data exist to describe in vitro patterns of cross resistance among large collections of clinical Aspergillus, including species other than A. fumigatus. We examined 771 Aspergillus spp. clinical isolates collected from 2000-2006 as part of a global antifungal surveillance program (553 A. fumigatus, 76 A. flavus, 59 A. niger, 35 A. terreus, 24 A. versicolor, and 24 other Aspergillus species). Antifungal susceptibility testing was performed by the Clinical and Laboratory Standards Institute (CLSI) M38-A broth dilution method against itraconazole( ITR), posaconazole (POS), ravuconazole (RAV) and voriconazole (VOR). We examined the potential for cross-resistance using measures of correlation overall and by species. Most Aspergillus had MICs of 2 microg/mL to VOR or POS remain extremely rare (
Risk Management of Simvastatin or Atorvastatin Interactions with CYP3A4 Inhibitors.
Drug Saf. 2008; 31(7): 587-96
Molden E, Skovlund E, Braathen P
BACKGROUND: Co-administration of cytochrome P450 (CYP) 3A4 inhibitors with simvastatin or atorvastatin is associated with increased risk of developing myopathy or rhabdomyolysis. OBJECTIVE: To detect co-prescriptions of CYP3A4 inhibitors with simvastatin or atorvastatin in community pharmacies and assess the risk-preventive actions taken by the prescribing physicians who were alerted about the co-prescription by the pharmacist. METHODS: This naturalistic study was performed during four separate 6-week periods in 2004 and 2005, and involved 110 Norwegian community pharmacists (25-30 in each period). Co-prescription of the selected CYP3A4 inhibitors diltiazem, verapamil, clarithromycin, erythromycin, fluconazole, itraconazole and ketoconazole with either simvastatin or atorvastatin was detected with the aid of a simple computer programme. In instances where the pharmacist alerted the prescribing physician about the co-prescription, information on possible strategies to minimize the risk associated with the interaction was also provided. Odds ratios (ORs) were estimated to describe the associations between prescription variables and frequencies of physician information and prescription change, respectively. RESULTS: In total, 245 co-prescriptions of CYP3A4 inhibitors with simvastatin (134 events) or atorvastatin (111) were detected. Diltiazem (86 events), verapamil (72), erythromycin (48) and clarithromycin (29) were the most commonly co-prescribed CYP3A4 inhibitors. Physicians were informed in 168 out of 245 cases (68.6%). The prescription was subsequently changed in 100 out of 168 cases (59.5%). Another 50 physicians (29.8%) responded that they would consult the patient and monitor potential adverse effects, while only 18 physicians (10.7%) replied that they had already managed the interactions or considered the issue as irrelevant. The adjusted OR for the informing of the physician was 1.89 (95% CI 0.98, 3.63) in patients receiving a daily HMG-CoA reductase inhibitor ('statin') dose of >/=40 mg compared with patients receiving a statin dose of
Int J Pharm. 2008 May 14;
Yang W, Tam J, Miller DA, Zhou J, McConville JT, Johnston KP, Williams RO
A nebulized dispersion of amorphous, high surface area, nanostructured aggregates of itraconazole (ITZ):mannitol:lecithin (1:0.5:0.2, w/w) yielded improved bioavailability in mice. The ultra-rapid freezing (URF) technique used to produce the nanoparticles was found to molecularly disperse the ITZ with the excipients as a solid solution. Upon addition to water, ITZ formed a colloidal dispersion suitable for nebulization, which demonstrated optimal aerodynamic properties for deep lung delivery and high lung and systemic levels when dosed to mice. The ITZ nanoparticles produced supersaturation levels 27 times the crystalline solubility upon dissolution in simulated lung fluid. A dissolution/permeation model indicated that the absorption of 3mum ITZ particles is limited by the dissolution rate (BCS Class II behavior), while absorption is permeation-limited for more rapidly dissolving 230nm particles. The predicted absorption half-life for 230nm amorphous ITZ particles was only 15min, as a result of the small particle size and high supersaturation, in general agreement with the in vivo results. Thus, bioavailability may be enhanced, by decreasing the particle size to accelerate dissolution and increasing permeation with (1) an amorphous morphology to raise the drug solubility, and (2) permeability enhancers.
Spherules, Hyphae, and Air-Crescent Sign.
Am J Med Sci. 2008 Jun; 335(6): 504-506
Tonelli AR, Khalife WT, Cao M, Young VB
Coccidioidomycosis is endemic in the southwestern United States, resulting in 100,000 infections annually. The majority of these infections are asymptomatic or manifest as community-acquired pneumonia. In rare cases, patients can present with a mononuclear-cell predominant pyopneumothorax. The presence of spherules in tissue specimens is pathognomonic of this condition. A 72-year-old man born in Arizona with a heavy smoking history, presented with a 1-month history of weakness, night sweats, exertional dyspnea, and left pleuritic chest pain. The physical examination was remarkable for decreased breath sounds and dullness to percussion at the left lung base. His initial laboratory examination showed leukocytosis, eosinophilia, and elevated C-reactive protein. Computed tomography of the chest revealed a left lower lobe infiltrate, a cavity with air-crescent sign and hydropneumothorax. The pleural fluid was sampled and revealed an eosinophilic exudate with normal pH. Bacterial and fungal cultures of the pleural fluid were negative. Biopsy of the cavity wall showed chronic inflammation, fungal hyphae, and rare spherule-like structures. The surgical specimen culture grew Coccidioides immitis. Complement fixation for coccidioidomycosis performed on a serum sample was positive at a titer of 1:2 but a latex agglutinin test was negative. The patient was diagnosed with chronic fibrocavitary pneumonia with pyopneumothorax secondary to C. immitis infection and discharged on itraconazole for 1 year. Coccidioidomycosis can present in a variety of forms and should be part of the differential diagnosis in patients presenting with cavitation, air-crescent sign, eosinophilic pleural effusion, and hyphae and spherules on the tissue specimen. Chronic fibrocavitary pneumonia should be especially considered in patients who lived in endemic areas and have risk factors such as diabetes mellitus or pulmonary fibrosis related to smoking.