Search results for: itraconazole

Authors: Yuvraj Singh Dangi, Kamta Prasad Namdeo, Surendra Bodhake

Abstract:

The purpose of this research was to develop and evaluate mucoadhesive films for buccal administration of itraconazole using film-forming and mucoashesive polymers. Buccal films of chitosan bearing Itraconazole were prepared by solvent casting technique. The films have been evaluated in terms of film weight, thickness, density, surface pH, FTIR, X-ray diffraction analysis, bioadhesion, swelling properties, and in vitro drug release studies. It was found that film formulations of 2 cm2 size having weight in the range of 204 ± 0.76 to 223 ± 2.09 mg and film thickness were in the range of 0.44 ± 0.11 to 0.57 ± 0.19 mm. Density of the films was found to be 0.102 to 0.126 g/ml. Drug content was found to be uniform in the range of 8.23 ± 0.07 to 8.73 ± 0.09 mg/cm2 for formulation A1 to A4. Maximum bioadhesion force was recorded for HPMC buccal films (A2) i.e. 0.57 ± 0.47 as compared to other films. In vitro residence time was in range of 1.7 ± 0.12 to 7.65 ± 0.15 h. The drug release studies show that formulations follow non-fickian diffusion. These mucoadhesive formulations could offer many advantages in comparison to traditional treatments.

Keywords: biovariability, buccal patches, itraconazole, Mucoadhesion

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Authors: S. Ataei, F. Sarrafzadeh Javadi, K. Gilani, E. Moazeni

Abstract:

Drug delivery systems using colloidal particulate carriers such as niosomes or liposomes have distinct advantages over conventional dosage forms because the particles can act as drug-containing reservoirs. These carriers play an increasingly important role in drug delivery. Niosomes are vesicular delivery systems which result from the self-assembly of hydrated surfactant. Niosomes are now widely studied as an attractive to liposomes because they alleviate the disadvantages associated with liposomes, such as chemical instability, variable purity of phospholipids and high cost. The encapsulation of drugs in niosomes can decrease drug toxicity, increase the stability of drug and increase the penetrability of drug in the location of application, and may reduce the dose and systemic side effect. Nowadays, Niosomes are used by the pharmaceutical industry in manufacturing skin medications, eye medication, in cosmetic formulas and these vesicular systems can be used to deliver aspiratory drugs. One way of improving dispersion in the water phase and solubility of the hydrophobic drug is to formulate in into niosomes. Itraconazole (ITZ) was chosen as a model hydrophobic drug. This drug is water insoluble (solubility ~ 1 ng/ml at neutral pH), is a broad-spectrum triazole antifungal agent and is used to treat various fungal disease. This study aims to investigate the capability of forming itraconazole niosomes with Spans, Tweens, Brijs as non-ionic surfactants. To this end, various formulations of niosomes have been studied with regard to parameters such as the degree of containment and particle size.

Keywords: physicochemical, non-ionic surfactant vesicles, itraconazole

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Authors: Milijana N. Miljkovic, Viktorija M. Dragojevic-Simic, Nemanja K. Rancic, Vesna M. Jacevic, Snezana B. Djordjevic, Momir M. Mikov, Aleksandra M. Kovacevic

Abstract:

Itraconazole (ITZ) is a weak base and extremely lipophilic compound, with water solubility as a rate-limiting step in its absorption from the gastrointestinal tract. Its absolute bioavailability, about 55%, is maximal when its oral formulation, capsules, are taken immediately after a full meal. Peak plasma concentrations (Cmax) are reached within 2 to 5 hrs after their administration. ITZ undergoes extensive hepatic metabolism by human CYP3A4 isoenzyme and more than 30 different metabolites have been identified. One of the main ones is hydroxyitraconazole (HITZ), in which plasma concentrations are almost twice higher than those of ITZ. Gender differences in drug PK (Pharmacokinetics) have already been recognized, but variations in metabolism are believed to be their major cause. The aim of the study was to investigate the influence of gender on ITZ PK parameters after administration of oral capsule formulation, following 100 mg single dosing in healthy adult volunteers under fed conditions. The single-center, open-label PK study was performed. PK analyses included PK parameters obtained after a single 100 mg dose administration of itraconazole capsules to 48 females and 66 males. Blood samples were collected at pre-dose and up to 72.0 h after administration (1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 12.0, 24.0, 36.0 and 72.0 hrs). The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxyitraconazole, were Cmax, AUClast, and AUCtot. Plasma concentrations of ITZ and HITZ were determined using a validated liquid chromatographic method with mass spectrometric detection, while pharmacokinetic parameters were estimated using non-compartmental methods. The pharmacokinetic analyses were performed using Kinetica software version 5.0. The mean value of ITZ Cmaxmen was 74.79 ng/ml, and Cmaxwomen was 51.291 ng/ml (independent samples test; p = 0.005). Hydroxyitraconazole had a mean value of Cmaxmen 106.37 ng/ml, and the mean value Cmaxwomen was 70.05 ng/ml. Women had, on average, lower AUClast and Cmax than men. AUClastmen for ITZ was 736.02 ng/mL*h and AUClastwomen was 566.62 ng/mL*h, while AUClastmen for HITZ was 1154.80 was ng/mL*h and AUClastwomen for HITZ was 708.12 ng/mL*h (independent samples test; p = 0.033). The mean values of ITZ AUCtotmen were 884.73 ng/mL*h and AUCtotwomen was 685.10 ng/mL*h. AUCtotmen for HITZ was 1290.41 ng/mL*h, while AUCtotwomen for HIZT was 788.60 ng/mL*h (p < 0.001). The results could point out to lower oral bioavailability of ITZ in women, since values of Cmax, AUClast, and AUCtot of both ITZ and HITZ were significantly lower in women than in men, respectively. The reason may be higher expression and activity of CYP3A4 in women than in men, but there also may be differences in other PK parameters. High variability of both ITZ and HITZ concentrations in both genders confirmed that ITZ is a highly variable drug. Further examinations of its PK are needed to justify strategies for therapeutic drug monitoring in patients treated by this antifungal agent.

Keywords: itraconazole, gender, hydroxyitraconazole, pharmacokinetics

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Authors: Nasrin Amirrajab, Yasaman Razavi Ghahfarokhi, Zahra Tootak, Maryam Hadian, Fatemeh Abooali Shamshiri

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Urinary tract infections (UTIs) have been reported in children with nephrotic syndrome. However, the only causes for the infection reported to date are bacteria, but not many prior reported occurrences of fungi or yeast as causative organisms. Hence, the present study aimed to describe the epidemiology of urinary tract fungal infections in a tertiary care pediatric. A single-center cross-sectional study was conducted at the nephrology ward of Aboozar Pediatric Hospital between March 21, 2021, and April 28, 2022. Urine was collected aseptically from children, inoculated onto culture media, and incubated at 37 °C for 18–48 hours. Yeast was identified following standard procedures. Antifungal susceptibility testing was determined by the disk diffusion method according to the CLSI guideline. Descriptive statistics and logistical regressions were used to estimate the crude ratio with a 95% confidence interval. P-value < 0.05 was considered significant. Among 68 individuals referred to the mycology lab, the result of direct examination and culture of all patients approved for C.albicans. Of these, 38 individuals (55.8%) were male, and 30 (44.2%) were female. The patients' age ranges were between one month and an 18-year-old. In the study of infection intensity, the patients were classified into three levels such as few (73.5%), moderate (20.6%), and many (5.9%). In the present study, all the patients were sensitive to Posaconazole. Also, the eagle effect was found in Amphotericin B, Voriconazole, and Fluconazole with frequencies of 91.7%, 91.7%, and 83%, respectively. In addition, just 8.3% of isolates were resistant to Itraconazole. It has not shown resistance in other mentioned medicine. The patients showed an intermediate response to Itraconazole (91.7%), Fluconazole (17%), Voriconazole (8.3%), and Amphotericin B (8.3%). There is a high prevalence of yeast infections in children with suspected UTIs. Also, boys are more likely to get yeast infections, and the severity of the infection is higher than girls. The present study demonstrated the importance of diagnosing and selecting the appropriate drug for urinary tract fungal infections in hospitalized children.

Keywords: urinary tract infections, children, fungal infections, yeast, antifungal susceptibility

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Authors: Anyimc, C. J. Aneke, J. O. Orji, O. Nworie, U. C. C. Egbule

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The microbial examination and antimicrobial susceptibility profile of microorganism isolated from the salt mining site in Ebonyi state were evaluated in the present study using a standard microbiological technique. A total of 300 samples were randomly collected in three sample groups (A, B, and C) of 100 each. Isolation, Identification and characterization of organization present on the soil samples were determined by culturing, gram-staining and biochemical technique. The result showed the following organisms were isolated with their frequency as follow: Bacillus species (37.3%) and Staphylococcus species(23.5%) had the highest frequency in the whole Sample group A and B while Klebsiella specie (15.7%), Pseudomonas species(13.7%), and Erwinia species (9.8%) had the least. Rhizopus species (42.0%) and Aspergillus species (26.0%) were the highest fungi isolated, followed by Penicillum species (20.0%) while Mucor species (4.0%), and Fusarium species (8.0%) recorded the least. Sample group C showed high microbial population of all the microbial isolates when compared to sample group A and B. Disc diffusion method was used to determine the susceptibility of isolated bacteria to various antibiotics (oxfloxacin, pefloxacin, ciprorex, augumentin, gentamycin, ciproflox, septrin, ampicillin), while agar well diffusion method was used to determine the susceptibility of isolated fungi to some antifungal drugs (metronidazole, ketoconazole, itraconazole fluconazole). The antibacterial activity of the antibiotics used showed that ciproflux has the best inhibitory effect on all the test bacteria. Ketoconazole showed the highest inhibitory effect on the fungal isolates, followed by itraconazole, while metronidazole and fluconazole showed the least inhibitory effect on the entire test fungal isolates. Hence, the multiple drug resistance of most isolates to appropriate drugs of choice are of great public health concern and cells for periodic monitoring of antibiograms to detect possible changing patterns. Microbes isolated in the salt mining site can also be used as a source of gene(s) that can increase salt tolerance in different crop species through genetic engineering.

Keywords: microorganisms, antibacterial, antifungal, resistance, salt mining site, Ebonyi State

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Authors: Isa Shu’aibu, A. A. Mu’inat, F. U. Maigari, M. A. Mani

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Candida albicans is the common cause of both oral and vaginal candidiasis in humans. This candidiasis leads to a wide range of physical, psychological and even physiological problems in humans particularly pregnant women. Samples of endocervical and high vaginal swab were collected from 200 women attending Gombe Specialist Hospital and inoculated on Saboraud Dextrose Agar (SDA) incorporated with chloramphenicol to get rid of the unwanted bacterial contaminants. Gram staining technique and germ tube test were employed for the identification, as Candida albicans is positive for both. Gram positive samples were 70% (n=140) and were further subjected to germ tube test. The remaining 30% (n=60) were found to be Gram negative. 90% (n=126) of the Gram positive ones isolated were also found to be positive for germ tube test; confirming the presence of Candida albicans. Antifungal susceptibility testing revealed that members of Imidazole (Ketoconazole, Miconazole) and those of Triazoles (Fluconazole and Itraconazole) were found to be more effective at concentrations of 20, 50 and 100 µg/disc compared to Griseofulvin (Fulcin) with only 26.00 mm zone of inhibition at 100 µg/disc concentration.

Keywords: Candida albicans, candidiasis, endocervical, vaginal swab, antifungal susceptibility, imidazole, triazoles

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Authors: David Oluwole Moses, Odeyemi Adebowale Toba, Olawale Adetunji Kola

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Candida auris, an emerging fungus, has been reported in more than 30 countries around the world since its first detection in 2009. Due to its several virulence factors, resistance to antifungals, and persistence in hospital settings, Candida auris has been reported to cause treatment-failure infections. This study was therefore carried out to determine the incidence of Candida auris in a tertiary hospital in Ekiti State, Nigeria. In this study, a total of 115 samples were screened for Candida species using cultural and molecular methods. The carriage of virulence factors and antifungal resistance among C. auris was detected using standard microbiological methods. Candida species isolated from the samples were 15 (30.0%) in clinical samples and 22 (33.85%) in hospital equipment screened. Non-albicans Candida accounted for 3 (20%) and 8 (36.36%) among the isolates from the clinical samples and equipment, respectively. Only five of the non-albicans Candida isolates were C. auris. All the isolates produced biofilm, gelatinase, and hemolysin, while none produced germ tubes. Two of the isolates were resistant to all the antifungals tested. Also, all the isolates were resistant to fluconazole and itraconazole. Nystatin appeared to be the most effective among the tested antifungals. The isolation of Candida auris is being reported for the second time in Nigeria, further confirming that the fungus has spread beyond Lagos and Ibadan, where it was first reported. The extent of the spread of the nosocomial fungus needed to be further investigated and curtailed in Nigeria before its outbreak in healthcare facilities.

Keywords: candida auris, virulence factors, antifungals, pathogen, hospital, infection

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Authors: Mariem Meddeb Sidhom, Souhayel Hedfi, Rjaibia Houda, Mehdi Dridi, Mohamed Ali Yousfi, Sâadia Gargouri

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Considering the important increase in costs of caspofungin treatments and ahead the evolution of its indication, pharmacy department was prompted to realize a review of the adequacy of prescriptions in the medical intensive care units (ICU). A retrospective observational study was conducted in Tunis military hospital concerning ICU prescriptions of caspofungin from 2008 until 2013. A pharmacist had returned to the patient’s medical records to collect data and to the microbiology department for parasitological results. The adequacy of prescriptions was evaluated by a pharmacist and an infectiologist parasitologist, referring to predefined scale of criteria resuming the indications of the marketing authorization (MA) and grade AI-AII of the guidelines of the Infectious Diseases Society of America (IDSA). Sixty two ICU patients have been treated with caspofungin during the period of study; however, 8 files were lost. Thus, 54 patients were included in the study having received 55 prescriptions of caspofungin. Males were a majority with 64.8% of the population. Mean age was 51 years. Caspofungin was indicated in accordance with the IDSA recommendations in 43.6% of the cases. The most case of non respect to the guidelines was the indication of caspofungin as empirical treatment in non neutropenic patients. Caspofungin was utilized as a first line treatment in 9 cases where it was possible to give fluconazole first, as germs were fluconazole- sensitive. Caspofungin was indicated in 2 patients with good renal function and in which nor amphotericin B, liposomal ampho B neither itraconazole had been previously used, as indicates the MA. The posology of caspofungin was respected in all prescriptions with a loading dose of 70 mg in the first day and a maintenance dose of 50 mg daily. Seven patients had received a daily dose of 70 mg, the recommended dose for people weighing more than 80 Kg. Caspofungin prescriptions are far to be adequately done. There is a clear need of optimization in indicating this molecule and that must be done in collaboration between the pharmacy department, the ICUs and parasitology department.

Keywords: caspofungin, prescription, intensive care units, marketing authorization, Tunisian hospital cohort

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Authors: Zorica Tomičić, Ružica Tomičić, Peter Raspor

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Growing resistance of pathogenic yeast Candida glabrata to many classes of antifungal drugs has stimulated efforts to discover new agents to combat a rising number of invasive C. glabrata infections, which deserves a great deal of concern due to the high mortality rate in immunocompromised populations. One promising strategy is the use of probiotic microorganisms, which, when administered in adequate amounts, confers a health benefit. A selected number of probiotic organisms, Saccharomyces boulardii among them, have been tested as potential biotherapeutic agents. The aim of this study was to investigate the effect of the probiotic yeast S. boulardii on the adhesion of clinical isolates of C. glabrata at different temperatures, pH values, and in the presence of three clinically important antifungal drugs, such as fluconazole, itraconazole and amphotericin B. The method used to assess adhesion was crystal violet staining. The selection of antimycotics concentrations used in the adhesion assay was based on minimum inhibitory concentrations (MICs) obtained by the preliminarily performed microdilution modification of the Reference method for broth dilution antifungal susceptibility testing of yeast (Clinical and Laboratory Standards Institute (CLSI), standard M27-A2). the results showed that despite the nonadhesiveness of S. boulardii cells, probiotic yeast significantly suppressed the adhesion of C. glabrata strains. Besides, at specific strain ratios, a slight stimulatory effect was observed in some C. glabrata strains, which highlights the importance of strain specificity and opens up further research interests. When environmental conditions are considered, temperature and pH significantly influenced co-culture adhesion of C. glabrata and S. boulardii. The adhesion of C. glabrata strains was relatively equally reduced over all tested temperature range (28°C, 37°C, 39°C and 42°C) in the presence of S. boulardii cells, while the adhesion of a few C. glabrata strains were significantly stimulated at 28°C and suppressed at 42°C. Further, the adhesion was highly dependent on pH, with the highest adherence at pH 4 and lowest at pH 8.5. It was observed that S. boulardii did not manage to suppress the adhesion of C. glabrata strains at high pH. Antimycotics on the other hand showed a greater impact, since S. boulardii failed to affect co-culture adhesion at higher antimycotics concentrations. As expected, exposure to various concentrations of amphotericin B significantly reduced the adherence ability of C.glabrata strains both in a single culture and co-culture with S. boulardii. Therefore, it can be speculated that S. boulardii could substitute the effect of antimycotics in a range concentrations and with specific type of strains. This would certainly change the view on the treatment of yeast infections in the future.

Keywords: adhesion, antimycotics, candida glabrata, saccharomyces boulardii

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