Displaying publications 1 - 20 of 34 in total

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  1. Santhanam J, Yahaya N, Aziz MN
    Med J Malaysia, 2013 Aug;68(4):343-7.
    PMID: 24145264
    Resistance to antifungal agents has increased in Candida spp., especially in non-albicans species. Recent findings reported a strikingly low susceptibility in Candida spp. towards itraconazole in Malaysia. In this study, a colorimetric broth dilution method was utilized to determine the susceptibility of Candida spp. isolated in Kuala Lumpur Hospital within a six month period. A total of 82 isolates from blood, peritoneal and other fluids were tested against 8 antifungal agents using the Sensititre Yeast One method. These comprised of 32 (39%) C. albicans, 17 (20.7%) C. glabrata, 15 (18.3%) C. tropicalis, 13 (15.9%) C. parapsilosis, two (2.4%) C. sake and 1 (1.2%) each of C. pelliculosa, C. rugosa and Pichia etchellsii/carsonii. Overall, susceptibility of all isolates to caspofungin was 98.8%, amphotericin B, 97.6%; 5-flucytosine, 97.6%; voriconazole, 97.6%; posaconazole, 87.8%; fluconazole, 82.9%; ketoconazole, 79.3%; and itraconazole, 56.1%. A total of 18 Candida spp. isolates (22 %) were resistant to at least one antifungal agent tested, and half of these were resistant to three or more antifungal agents. C. glabrata was the most frequently identified resistant species (10 isolates), followed by C. tropicalis (4 isolates), C. parapsilosis (3 isolates) and C. albicans (1 isolate). Resistance was highest against ketoconazole (20.9%), followed by itraconazole (13.4%). However, 30.5% of isolates were susceptible-dose dependent towards itraconazole. Long-term usage of itraconazole in Malaysia and a predominance of nonalbicans species may account for the results observed in this study. In conclusion, susceptibility to antifungal drugs is species-dependent among Candida spp.; reduced susceptibility to itraconazole is concomitant with the high number of non-albicans Candida species isolated in Malaysia.
    Matched MeSH terms: Itraconazole*
  2. Rao K, Abdullah M, Ahmed U, Wehelie HI, Shah MR, Siddiqui R, et al.
    Arch Microbiol, 2024 Mar 04;206(4):134.
    PMID: 38433145 DOI: 10.1007/s00203-024-03854-3
    Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.
    Matched MeSH terms: Itraconazole/pharmacology
  3. Wong JW, Nisar UR, Yuen KH
    PMID: 14643517
    A sensitive and selective high-performance liquid chromatographic method was developed for the determination of itraconazole and its active metabolite, hydroxyitraconazole, in human plasma. Prior to analysis, both compounds together with the internal standard were extracted from alkalinized plasma samples using a 3:2 (v/v) mixture of 2,2,4-trimethylpentane and dichloromethane. The mobile phase comprised 0.02 M potassium dihydrogen phosphate-acetonitrile (1:1, v/v) adjusted to pH 3.0. Analysis was run at flow-rate of 0.9 ml/min with excitation and emission wavelengths set at 260 and 365 nm, respectively. Itraconazole was found to adsorb on glass or plastic tubes, but could be circumvented by prior treating the tubes using 10% dichlorodimethylsilane in toluene. Moreover, rinsing the injector port with acetonitrile helped to overcome any carry-over effect. This problem was not encountered with hydroxyitraconazole. The method was sensitive with limit of quantification of 3 ng/ml for itraconazole and 6 ng/ml for hydroxyitraconazole. The calibration curve was linear over a concentration range of 2.8-720 ng/ml for itraconazole and 5.6-720 ng/ml for the hydroxy metabolite. Mean recovery value of the extraction procedure for both compounds was about 85%, while the within-day and between-day coefficient of variation and percent error values of the assay method were all less than 15%. Hence, the method is suitable for use in pharmacokinetic and bioavailability studies of itraconazole.
    Matched MeSH terms: Itraconazole/blood*; Itraconazole/pharmacokinetics
  4. Lee WH, Loo CY, Ghadiri M, Leong CR, Young PM, Traini D
    Adv Drug Deliv Rev, 2018 08;133:107-130.
    PMID: 30189271 DOI: 10.1016/j.addr.2018.08.012
    Lung cancer is a highly invasive and prevalent disease with ineffective first-line treatment and remains the leading cause of cancer death in men and women. Despite the improvements in diagnosis and therapy, the prognosis and outcome of lung cancer patients is still poor. This could be associated with the lack of effective first-line oncology drugs, formation of resistant tumors and non-optimal administration route. Therefore, the repurposing of existing drugs currently used for different indications and the introduction of a different method of drug administration could be investigated as an alternative to improve lung cancer therapy. This review describes the rationale and development of repositioning of drugs for lung cancer treatment with emphasis on inhalation. The review includes the current progress of repurposing non-cancer drugs, as well as current chemotherapeutics for lung malignancies via inhalation. Several potential non-cancer drugs such as statins, itraconazole and clarithromycin, that have demonstrated preclinical anti-cancer activity, are also presented. Furthermore, the potential challenges and limitations that might hamper the clinical translation of repurposed oncology drugs are described.
    Matched MeSH terms: Itraconazole/administration & dosage; Itraconazole/therapeutic use*
  5. Yap FB
    Trans R Soc Trop Med Hyg, 2010 Feb;104(2):168-9.
    PMID: 19766279 DOI: 10.1016/j.trstmh.2009.05.016
    A retrospective study was conducted to determine the clinical characteristics and treatment outcomes of 11 new patients with a histological diagnosis of chromoblastomycosis at Sarawak General Hospital, Malaysia, between 1996 and 2008. The majority (81.8%) were males, and the median age at presentation was 40 years. Over half the patients were farmers. All the patients had irregular verrucous lesions, mostly on the lower limbs (90.9%), and had initially been misdiagnosed. The mean duration of the lesions was 13.8 years. Oral terbinafine and itraconazole were administered to all the patients; clinical cure was seen in 54.5%, and partial response in 18.2%. Concomitant electrocautery and cryotherapy were only effective for small lesions.
    Matched MeSH terms: Itraconazole/therapeutic use
  6. NoorZurani MH, Vicknasingam B, Narayanan S
    Drug Alcohol Rev, 2009 Nov;28(6):688-90.
    PMID: 19930027 DOI: 10.1111/j.1465-3362.2009.00128.x
    Methadone, a pharmacological agent used to treat heroin dependence is relatively safe, but may cause cardiac arrhythmias in the concurrent presence of other risk factors. APPROACH AND KEY FINDINGS: This case report highlights the risk of torsade de pointes, a life-threatening cardiac arrhythmia, in a heroin-dependent patient receiving methadone substitution therapy who was prescribed itraconazole for vaginal thrush. The patient presented to the accident and emergency department for chest discomfort and an episode of syncope following two doses of itraconazole (200 mg). Electrocardiogram monitoring at the accident and emergency department showed prolonged rate-corrected QT interval leading to torsade de pointes. The patient was admitted for cardiac monitoring, and electrocardiogram returned to normal upon discontinuation of methadone.
    Matched MeSH terms: Itraconazole/adverse effects*
  7. Yap FB
    Int J Infect Dis, 2010 Jun;14(6):e543-4.
    PMID: 19889559 DOI: 10.1016/j.ijid.2009.07.005
    Matched MeSH terms: Itraconazole/administration & dosage
  8. Lachmanan SR, Haniza O, Hisham AN, Subramaniam J, Merican I
    Ann Acad Med Singap, 2001 Nov;30(6):656-8.
    PMID: 11817299
    INTRODUCTION: Bilateral adrenal enlargement is often the result of disseminated malignant disease, and this diagnosis is particularly likely in a patient with severe weight loss. We describe a case with bilateral adrenal enlargement presenting with progressively worsening backache as a prominent symptom.

    CLINICAL PICTURE: A 55-year-old man presented with intermittent low back pain which was progressively worsening, fever, anorexia, low back pain and a 10-kg weight loss. He had underlying diabetes mellitus and ischaemic heart disease. He gave a history of travel to caves for worship. Clinically, the most significant findings included nodular lesions in the anterior fauces and left palatoglossal region. Computed tomographic scan revealed bilateral adrenal masses. Biopsies were taken from the palatal nodules, which revealed histiocytes with numerous histoplasma organisms.

    TREATMENT: He was commenced on itraconazole 200 mg daily for a period of 9 months. There was a dramatic initial response with settling of his fever and this was followed by subjective improvement in his well-being.

    OUTCOME: He is presently on follow-up and has completed 9 months of itraconazole therapy with resolution of all his symptoms and has gained about 10 kg of weight.

    Matched MeSH terms: Itraconazole/therapeutic use
  9. Chow KW, Ting HC, Yap YP, Yee KC, Purushotaman A, Subramanian S, et al.
    Int J Dermatol, 1998 Jun;37(6):446-8.
    PMID: 9646134
    Matched MeSH terms: Itraconazole/administration & dosage*
  10. Ng KP, Soo-Hoo TS, Na SL, Gan GG, Sangkar JV, Teh AKH
    Med J Malaysia, 2003 Oct;58(4):608-12.
    PMID: 15190640
    Scopulariopsis brevicaulis is a soil fungus normally associated with onychomycosis. It causes subcutaneous infection in immunocompromised patients and is rarely isolated from blood. A case of systemic Scopulariopsis brevicaulis infection was reported in a patient with acute myeloid leukemia. The patient developed persistent fever that did not respond to wide spectrum antibiotics and amphotericin B. Scopulariopsis brevicaulis was the only pathogen isolated from blood cultures. The fever subsided with itraconazole and there was no recurrence of fungal infection with prolonged maintenance of oral itraconazole.
    Matched MeSH terms: Itraconazole/therapeutic use*
  11. Long CM, Tang K, Chokshi H, Fotaki N
    AAPS PharmSciTech, 2019 Feb 13;20(3):113.
    PMID: 30761437 DOI: 10.1208/s12249-019-1317-z
    The aim of this study is to investigate the dissolution properties of poorly soluble drugs from their pure form and their amorphous formulation under physiological relevant conditions for oral administration based on surface dissolution ultraviolet (UV) imaging. Dissolution of two poorly soluble drugs (cefuroxime axetil and itraconazole) and their amorphous formulations (Zinnat® and Sporanox®) was studied with the Sirius Surface Dissolution Imager (SDI). Media simulating the fasted state conditions (compendial and biorelevant) with sequential media/flow rate change were used. The dissolution mechanism of cefuroxime axetil in simulated gastric fluid (SGF), fasted state simulated gastric fluid (FaSSGF) and simulated intestinal fluid (SIF) is predominantly swelling as opposed to the convective flow in fasted state simulated intestinal fluid (FaSSIF-V1), attributed to the effect of mixed micelles. For the itraconazole compact in biorelevant media, a clear upward diffusion of the dissolved itraconazole into the bulk buffer solution is observed. Dissolution of itraconazole from the Sporanox® compact is affected by the polyethylene glycol (PEG) gelling layer and hydroxypropyl methylcellulose (HPMC) matrix, and a steady diffusional dissolution pattern is revealed. A visual representation and a quantitative assessment of dissolution properties of poorly soluble compounds and their amorphous formulation can be obtained with the use of surface dissolution imaging under in vivo relevant conditions.
    Matched MeSH terms: Itraconazole/chemistry*
  12. Choon SE, Khoo JJ
    Br J Dermatol, 1999 Mar;140(3):557-8.
    PMID: 10233296
    Matched MeSH terms: Itraconazole/therapeutic use*
  13. Tay ST, Tanty Haryanty T, Ng KP, Rohani MY, Hamimah H
    Mycoses, 2006 Jul;49(4):324-30.
    PMID: 16784448
    The in vitro susceptibilities of Malaysian clinical isolates of Cryptococcus neoformans var. grubii and C . gattii to five antifungal drugs (amphotericin B, flucytosine, fluconazole, itraconazole and ketoconazole) were determined using the Etest method. None of the Malaysian isolates was resistant to amphotericin B and ketoconazole. Isolates resistant to flucytosine, fluconazole and itraconazole were observed in this study. Minimum inhibition concentrations (MICs) of > or = 32 microg ml(-1) against flucytosine, > or = 64 microg ml(-1) against fluconazole and > or = 1 microg ml(-1) against itraconazole were noted in four (8.3%), two (4.2%) and one (2.1%) isolates respectively. There was no significant difference in the MICs for both Cryptococcus species (P > 0.05), indicating that C. gattii was as susceptible as var. grubii to all the antifungal drugs tested. No significant difference in the MICs for both Cryptococcus species collected from 1980 to 1990 and 2002 to 2004 were observed (P > 0.05).
    Matched MeSH terms: Itraconazole/pharmacology
  14. Lim WM, Rajinikanth PS, Mallikarjun C, Kang YB
    Int J Nanomedicine, 2014;9:2117-26.
    PMID: 24833900 DOI: 10.2147/IJN.S57565
    The objectives of this study were to develop and characterize itraconazole (ITZ)-loaded nanostructured lipid carriers (NLCs) and to study their potential for drug delivery into the brain. Precirol(®) ATO 5 and Transcutol(®) HP were selected as the lipid phase, and Tween(®) 80 and Solutol(®) HS15 as surfactants. The ITZ-NLCs were prepared by a hot and high-pressure homogenization method. The entrapment efficiency for the best formulation batch was analyzed using high-performance liquid chromatography and was found to be 70.5%±0.6%. The average size, zeta potential, and polydispersity index for the ITZ-NLCs used for animal studies were found to be 313.7±15.3 nm, -18.7±0.30 mV, and 0.562±0.070, respectively. Transmission electron microscopy confirmed that ITZ-NLCs were spherical in shape, with a size of less than 200 nm. Differential scanning calorimetry and X-ray diffractometry analysis showed that ITZ was encapsulated in the lipid matrix and present in the amorphous form. The in vitro release study showed that ITZ-NLCs achieved a sustained release, with cumulative release of 80.6%±5.3% up to 24 hours. An in vivo study showed that ITZ-NLCs could increase the ITZ concentration in the brain by almost twofold. These results suggest that ITZ-NLCs can be exploited as nanocarriers to achieve sustained release and brain-targeted delivery.
    Matched MeSH terms: Itraconazole/administration & dosage*; Itraconazole/pharmacokinetics*
  15. Siew HH
    Nihon Ishinkin Gakkai Zasshi, 2017;58(3):E107-E113.
    PMID: 28855477 DOI: 10.3314/mmj.17.014
    Feline sporotrichosis has been reported in Malaysia since the 1990's. Since then, studies have revealed that clinical clade D, Sporothrix schenckii sensu stricto, of a single clonal strain is the most common cause of this disease in Malaysia. The prevalence of a single clonal strain from a clinical clade was never before reported in Asia in a specific geographical niche. This raises the possibility of a process of purifying selection and subsequent clonal proliferation. While agricultural practices may serve as the selective pressure, direct causality has yet to be established. Studies into the thermo-tolerability of the Malaysian clonal strain of S. schenckii sensu stricto revealed that a small minority of clinical isolates have the capacity to grow at 37℃, while the majority displayed low susceptibility to commonly used antifungals in clinical practice, such as itraconazole (ITZ) and terbinafine (TRB). Despite unestablished breakpoints, suspected resistance (MIC > 4 mg/mL) towards amphotericin B (AMB) and fluconazole (FLC) was recorded in the isolates. This explains the often lack of clinical response in feline patients treated with recommended doses of antifungals, including ITZ. Coupled with the potential zoonotic transmission to clients and veterinarians, protracted treatment period, and subsequent cost of treatment, prognosis of feline sporotrichosis is often regarded to be poor. The use of a higher dose of ITZ has been reported, and an adoption of this high-dose treatment regime is reported in this manuscript, with complete cure achieved in cases of recalcitrant and/or unresponsive feline sporotrichosis, which would otherwise be euthanized.
    Matched MeSH terms: Itraconazole/administration & dosage; Itraconazole/pharmacology
  16. Ding CH, Tzar MN, Rahman MM, Muttaqillah NA, Redzuan SR, Periyasamy P
    Pak J Med Sci, 2014 Jul;30(4):914-6.
    PMID: 25097544
    Fungaemia due to Paecilomyces lilacinus is generally not considered in AIDS patients because this condition is not categorised as an AIDS-indicator illness. We report a case of a 25-year-old lady who presented to our hospital with Guillain-Barré Syndrome, with the subsequent development of refractory fungaemia, multi-organ failure and disseminated intravascular coagulopathy. Amphotericin B was given as empirical antifungal therapy. HIV screening was reactive and Paecilomyces lilacinus was isolated from her blood. The fungaemia did not resolve after one week of amphotericin B treatment. The addition of itraconazole was also unsuccessful in clearing the fungaemia. Accurate mycological diagnosis is important in the care of AIDS patients with fungaemia because of the risk of treatment failure with empirical therapy.
    Matched MeSH terms: Itraconazole
  17. Marsilla MM, Khairunisa AA, Azyani Y, Petrick P
    Malays J Pathol, 2019 Aug;41(2):223-227.
    PMID: 31427560
    INTRODUCTION: Histoplasmosis can present in a myriad of clinical manifestations, which often makes its diagnosis difficult and occasionally, deceptive.

    CASE REPORT: We describe a case of a 33 years old gentleman who was clinically diagnosed as acute appendicitis at initial presentation in view of a one-week history of fever, right lower quadrant abdominal pain- and guarding at right iliac fossa. He had thrombocytopenia and lymphopenia on presentation. Mesenteric lymphadenitis and small bowel lesion were found intraoperatively, which was respectively biopsied and resected. Histopathological result confirms disseminated histoplasmosis. Retroviral screen was positive. He was treated with amphotericin B for one week, subsequently switched to oral itraconazole, followed by initiation of highly active antiretroviral therapy (HAART).

    DISCUSSION: This case illustrates the various nature of histoplasmosis presentation. A high index of suspicion is needed to clinch the diagnosis and subsequently institute prompt treatment as disseminated disease can be fatal if left untreated in an immunosuppressed host.

    Matched MeSH terms: Itraconazole
  18. Suresh Kumar
    MyJurnal
    Introduction: Tuberculosis (TB) is one of the utmost serious infectious diseases worldwide. The emergence of multi- drug resistance demands the development of better or new putative drug targets for tuberculosis. Recent studies sug- gest Mycobacterium tuberculosis cytochrome P450 enzymes as promising drug targets and azole drugs as potential inhibitors. Methods: Various computational tools, like Expasy Protparam, Swiss model, RaptorX and Phyre2 were used to analyze 12 Mycobacterium tuberculosis P450 enzymes and determine their three-dimensional structure. The structural validation was done through a Ramachandran plot using RAMPAGE server. The docking of P450 enzymes with azole drugs was done with autodock ver 4.2.6. Results: Based on sub-cellular localization prediction using CEL- LO tool, P450 enzymes CYP123A1, CYP132A1, CYP135A1, CYP136A1, CYP140A1, and CYP143A1 were predicted to be in the cytoplasm. Through structure assessment by Ramachandran plot, the best homology modelled proteins were docked with azole drugs like clotrimazole, croconazole, econazole, fluconazole, itraconazole, itraconazole, ketaconazole and micronazole by using autodock. By docking method it is identified that ketaconazole drug has a high affinity towards most of the mycobacterium P450 enzymes followed by the itrconazole drug. CYP123A1 enzyme is preferable as a drug target due to high binding affinity towards ketoconazole followed by CYP135A1, CYP140A1 enzymes. Conclusion: This study would help in identifying putative novel drug targets in Mycobacterium tuberculosis, which can lead to promising candidates for the optimization and development of novel anti-mycobac- terial agents.
    Matched MeSH terms: Itraconazole
  19. Mohamad N, Badrin S, Wan Abdullah WNH
    Korean J Fam Med, 2018 Mar;39(2):126-129.
    PMID: 29629046 DOI: 10.4082/kjfm.2018.39.2.126
    Fixed cutaneous sporotrichosis is a differential diagnosis that can be considered in diabetic patients who present with a poorly healing ulcer. Although its prevalence is low, it can occur in patients with immunocompromised status. Here we report a case of a 70-year-old man with diabetes mellitus who presented with a 1-month history of an unhealed ulcer over the tip of his left middle finger. He experienced a cat bite over his left middle finger 1 month prior to the appearance of the lesion. A skin biopsy revealed the presence of Sporothrix schenckii. Oral itraconazole 200 mg twice daily was started empirically and the patient showed marked improvement in the skin lesion after 2 months of therapy.
    Matched MeSH terms: Itraconazole
  20. James JE, Lamping E, Santhanam J, Milne TJ, Abd Razak MF, Zakaria L, et al.
    Front Microbiol, 2020;11:272.
    PMID: 32296397 DOI: 10.3389/fmicb.2020.00272
    In the fungal pathogen Aspergillus fumigatus, resistance to azole antifungals is often linked to mutations in CYP51A, a gene that encodes the azole antifungal drug target lanosterol 14α-demethylase. The aim of this study was to investigate whether similar changes could be associated with azole resistance in a Malaysian Fusarium solani species complex (FSSC) isolate collection. Most (11 of 15) clinical FSSC isolates were Neocosmospora keratoplastica and the majority (6 of 10) of environmental isolates were Neocosmospora suttoniana strains. All 25 FSSC isolates had high minimum inhibitory concentrations (MICs) for itraconazole and posaconazole, low MICs for amphotericin B, and various (1 to >32 mg/l) voriconazole susceptibilities. There was a tight association between a 23 bp CYP51A promoter deletion and high (>32 mg/l) voriconazole MICs; of 19 FSSC strains sequenced, nine isolates had voriconazole MICs > 32 mg/l, and they all contained the 23 bp CYP51A promoter deletion, although it was absent in the ten remaining isolates with low (≤12 mg/l) voriconazole MICs. Surprisingly, this association between voriconazole resistance and the 23 bp CYP51A promoter deletion held true across species boundaries. It was randomly distributed within and across species boundaries and both types of FSSC isolates were found among environmental and clinical isolates. Three randomly selected N. keratoplastica isolates with low (≤8 mg/l) voriconazole MICs had significantly lower (1.3-7.5 times) CYP51A mRNA expression levels than three randomly selected N. keratoplastica isolates with high (>32 mg/l) voriconazole MICs. CYP51A expression levels, however, were equally strongly induced (~6,500-fold) by voriconazole in two representative strains reaching levels, after 80 min of induction, that were comparable to those of CYP51B. Our results suggest that FSSC isolates with high voriconazole MICs have a 23 bp CYP51A promoter deletion that provides a potentially useful marker for voriconazole resistance in FSSC isolates. Early detection of possible voriconazole resistance is critical for choosing the correct treatment option for patients with invasive fusariosis.
    Matched MeSH terms: Itraconazole
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