Displaying publications 1 - 20 of 34 in total

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  1. 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
  2. Yap FB, Thevarajah S, Asmah J
    Dermatol. Online J., 2010;16(7):2.
    PMID: 20673530
    Penicilliosis is a systemic fungal infection caused by Penicillium marneffei. The infection is most commonly seen in Southeast Asia, Southern China, Hong Kong, and Taiwan. It is rarely seen among individuals of African descent. Here, we report a case of penicilliosis in an African man from Namibia who was studying in Malaysia. He presented with multiple umbilicated papules associated with cough, fever, loss of appetite, and weight. He also had urethral discharge and admitted to unprotected sexual intercourse with multiple partners. Histopathological examination of a skin papule showed the presence of multiple 2 to 4 microm intracellular yeast cells. Culture of the papule revealed Penicillium marneffei. The serology for human immunodeficiency virus (HIV) was positive. This case illustrates the need to recognize penicilliosis in any individuals staying or travelling to Southeast Asia and the need to look for underlying HIV infection in adults with umbilicated papules.
    Matched MeSH terms: Itraconazole/therapeutic use
  3. 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*
  4. Tang MM, Tang JJ, Gill P, Chang CC, Baba R
    Int J Dermatol, 2012 Jun;51(6):702-8.
    PMID: 22607289 DOI: 10.1111/j.1365-4632.2011.05229.x
    Sporotrichosis is a subcutaneous fungal infection caused by a thermally dimorphic aerobic fungus, Sporothrix schenckii. It results from traumatic inoculation or contact with animals. Most cases were reported mainly in the tropics and subtropics.
    Matched MeSH terms: Itraconazole/therapeutic use
  5. 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*
  6. 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
  7. Chuah CH, Ong YC, Kong BH, Woo YY, Wong PS, Leong KN, et al.
    J R Coll Physicians Edinb, 2020 Jun;50(2):138-140.
    PMID: 32568283 DOI: 10.4997/JRCPE.2020.211
    Talaromycosis typically occurs as an opportunistic infection among immunocompromised individuals. Infection caused by species other than T. marneffei is uncommon. While most reported cases describe infection in the lungs, we report an extremely rare intracranial Talaromyces species infection. This 61-year-old with end-stage renal disease who was unwell for the previous two months, presented with fever and worsening confusion lasting for three days. Lumbar puncture was suggestive of meningitis. Cerebrospinal fluid (CSF) culture was later confirmed to be Penicillium chrysogenum. The patient was co-infected with Group B Streptococcus sepsis. He improved with amphotericin B and ceftriaxone and was discharged with oral itraconazole for four weeks. However, he died of unknown causes two weeks later at home. Talaromyces species infection in the central nervous system is uncommon. This case highlighted a rare but life-threatening fungal meningitis. Among the four reported cases worldwide, none of the patients survived.
    Matched MeSH terms: Itraconazole
  8. 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*
  9. 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
  10. Wang H, Xu YC, Hsueh PR
    Future Microbiol, 2016 10;11:1461-1477.
    PMID: 27750452
    In the Asia-Pacific region, Candida albicans is the predominant Candida species causing invasive candidiasis/candidemia in Australia, Japan, Korea, Hong Kong, Malaysia, Singapore and Thailand whereas C. tropicalis is the most frequently encountered Candida species in Pakistan and India. Invasive isolates of C. albicans, C. parapsilosis complex and C. tropicalis remain highly susceptible to fluconazole (>90% susceptible). Fluconazole resistance (6.8-15%), isolates with the non-wild-type phenotype for itraconazole susceptibility (3.9-10%) and voriconazole (5-17.8%), and echinocandin resistance (2.1-2.2% in anidulafungin and 2.2% in micafungin) among invasive C. glabrata complex isolates are increasing in prevalence. Moreover, not all isolates of C. tropicalis have been shown to be susceptible to fluconazole (nonsusceptible rate, 5.7-11.6% in China) or voriconazole (nonsusceptible rate, 5.7-9.6% in China).
    Matched MeSH terms: Itraconazole/therapeutic use
  11. Somchit N, Wong CW, Zuraini A, Ahmad Bustamam A, Hasiah AH, Khairi HM, et al.
    Drug Chem Toxicol, 2006;29(3):237-53.
    PMID: 16777703
    Itraconazole and fluconazole are potent wide spectrum antifungal drugs. Both of these drugs induce hepatotoxicity clinically. The mechanism underlying the hepatotoxicity is unknown. The purpose of this study was to investigate the role of phenobarbital (PB), an inducer of cytochrome P450 (CYP), and SKF 525A, an inhibitor of CYP, in the mechanism of hepatotoxicity induced by these two drugs in vivo. Rats were pretreated with PB (75 mg/kg for 4 days) prior to itraconazole or fluconazole dosing (20 and 200 mg/kg for 4 days). In the inhibition study, for 4 consecutive days, rats were pretreated with SKF 525A (50 mg/kg) or saline followed by itraconazole or fluconazole (20 and 200 mg/kg) Dose-dependent increases in plasma alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma-GT), and alkaline phosphatase (ALP) activities and in liver weight were detected in rats receiving itraconazole treatment. Interestingly, pretreatment with PB prior to itraconazole reduced the ALT and gamma-GT activities and the liver weight of rats. No changes were observed in rats treated with fluconazole. Pretreatment with SKF 525A induced more severe hepatotoxicity for both itraconazole and fluconazole. CYP 3A activity was inhibited dose-dependently by itraconazole treatment. Itraconazole had no effects on the activity of CYP 1A and 2E. Fluconazole potently inhibited all three isoenzymes of CYP. PB plays a role in hepatoprotection to itraconazole-induced but not fluconazole-induced hepatotoxicity. SKF 525A enhanced the hepatotoxicity of both antifungal drugs in vivo. Therefore, it can be concluded that inhibition of CYP may play a key role in the mechanism of hepatotoxicity induced by itraconazole and fluconazole.
    Matched MeSH terms: Itraconazole/toxicity*
  12. 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*
  13. Choon SE, Khoo JJ
    Br J Dermatol, 1999 Mar;140(3):557-8.
    PMID: 10233296
    Matched MeSH terms: Itraconazole/therapeutic use*
  14. 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
  15. 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*
  16. Mohd Nor F, Tan LH, Na SL, Ng KP
    Mycopathologia, 2015 Aug;180(1-2):95-8.
    PMID: 25739670 DOI: 10.1007/s11046-015-9879-0
    Rhodotorula species are increasingly being identified as a cause of fungal infection in the central nervous system, especially in patients with compromised immunity. The diagnosis could easily be missed due to low index of suspicion, as cryptococcus meningitis and cerebral toxoplasmosis are more common amongst immunocompromised hosts. To date, there are six cases of Rhodotorula-related meningitis reported, and three are associated with human immunodeficiency virus infection. In this report, a case of a Malaysian male with underlying human immunodeficiency virus infection who developed Rhodotorula mucilaginosa meningitis is presented. High-grade fever and severe headaches were the complaints presented in three previous case reports. India ink and nigrosin stainings were performed in the two previous reports and both revealed positive results. R. mucilaginosa were isolated from the culture of the patient's cerebrospinal fluid in all three previous reports. Predominant lymphocyte infiltration in the cerebrospinal fluid examination was documented in two reports. CD4 counts were above 100/µl in two previously published reports, while another report documented CD4 count as 56/µl. Amphotericin B and itraconazole are identified to be the first line of antifungal used and as the maintenance therapy, respectively. The possibility of relapse cannot be excluded as it was reported in the first report. It was also revealed that the current case has almost similar clinical presentation and therapeutic outcome as compared to the published reports, but some differences in diagnostic details were to be highlighted.
    Matched MeSH terms: Itraconazole/therapeutic use
  17. Manohar A, Nizlan MN
    Orthopedics, 2008 Jul;31(7):710.
    PMID: 19292371
    A 60-year-old man presented with a 3-month history of nonhealing ulcer over the tip of his right thumb. The ulcer started as a blister over the tip of the thumb that later ruptured and spread proximally to cover the whole pulp area of the thumb. There was no history of trauma, fever, weight loss, or loss of appetite. He is a pensioner and an avid gardener. He has a few cats as pets. The patient initially presented to a private orthopedic surgeon with a nonhealing ulcer of the right thumb. Multiple debridements were unsuccessful in ameliorating the ulcer. Three months after the onset of the initial lesion, multiple painless erythematous nodules had developed on his right arm, and one on the right thigh. All routine blood investigations were nondiagnostic. Swab culture from the ulcer failed to grow any organism and a course of antibiotics did not resolve the problem. Cultures of the biopsy specimen using Sabouraud's dextrose agar and potato carrot medium grew dark brown plaques that microscopically appeared to be branching hyphae. A diagnosis of sporotrichosis of the right upper limb was made and the patient was started on antifungal treatment immediately (T. Itraconazole [Sporanox] 200 mg BD). One month after commencement of antifungal treatment, the ulcer began to dry up and at 3 months all the lesions including the one on the right thigh had healed.
    Matched MeSH terms: Itraconazole/therapeutic use*
  18. Han HS, Kano R, Chen C, Noli C
    Vet Dermatol, 2017 Feb;28(1):156-e32.
    PMID: 28133872 DOI: 10.1111/vde.12417
    BACKGROUND: Feline sporotrichosis is common in Malaysia. Thermosensitivity and effects of azole treatment on fungal susceptibility are unknown.

    OBJECTIVES: To evaluate thermotolerance and antifungal susceptibility of feline Malaysian Sporothrix isolates, compare microdilution (MD) and E-test results, and investigate changes in susceptibility during azole therapy.

    METHODS: Sporothrix schenckii sensu stricto was isolated from 44 cats. Thermotolerance was determined via culture at 37°C for 7 days. Susceptibility to itraconazole (ITZ), ketoconazole (KTZ) and terbinafine (TRB) was assessed in 40 isolates by MD; to amphotericin B (AMB), KTZ, ITZ, fluconazole (FLC) and posaconazole (POS) by E-test. Results were statistically compared by Pearson's Product Moment. In eight ketoconazole treated cats, susceptibility testing to itraconazole and ketoconazole was repeated every two months for six months.

    RESULTS: Thermotolerance was observed in 36 of 44 (82%) isolates. Assuming that isolates growing at antifungal concentrations ≥4 mg/mL were resistant, all were resistant on E-test to FLC and AMB, 11 (28%) to POS, 6 (15%) to ITZ and 1 (3%) to KTZ. On MD, 27 of 40 (68%) were resistant to TRB, 2 (5%) to ITZ and 3 (8%) to KTZ. There was no correlation between E-test and MD results (KTZ r = 0.10, P = 0.54, and ITZ r = 0.11, P = 0.48). MD values for ITZ and KTZ did not exceed 4 mg/L during KTZ therapy.

    CONCLUSION: The majority of feline isolates in Malaysia are thermosensitive. Lack of correlation between E-test and MD suggests that the E-test is unreliable to test antifungal susceptibility for Sporothrix spp. compared to MD. KTZ was the antifungal drug with the lowest MIC. Prolonged KTZ administration may not induce changes in antifungal susceptibility.

    Matched MeSH terms: Itraconazole/therapeutic use
  19. Somchit N, Norshahida AR, Hasiah AH, Zuraini A, Sulaiman MR, Noordin MM
    Hum Exp Toxicol, 2004 Nov;23(11):519-25.
    PMID: 15625777
    Itraconazole and fluconazole are oral antifungal drugs, which have a wide spectrum antifungal activity and better efficacy than the older drugs. However, both drugs have been associated with hepatotoxicity in susceptible patients. The mechanism of antifungal drug-induced hepatotoxicity is largely unknown. Therefore, the aim of this present study was to investigate and compare the hepatotoxicity induced by these drugs in vivo. Rats were treated intraperitoneally with itraconazole or fluconazole either single (0, 10, 100 and 200 mg/kg) or subchronic (0, 10, 50 and 100 mg/kg per day for 14 days) doses. Plasma and liver samples were taken at the end of the study. A statistically significant and dose dependent increase of plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities were detected in the subchronic itraconazole-treated group. In addition, dose-dependent hepatocellular necrosis, degeneration of periacinar and mizonal hepatocytes, bile duct hyperplasia and biliary cirrhosis and giant cell granuloma were observed histologically in the same group. Interestingly, fluconazole treated rats had no significant increase in transaminases for both single and subchronic groups. In the subchronic fluconazole treated rats, only mild degenerative changes of centrilobular hepatocytes were observed. These results demonstrated that itraconazole was a more potent hepatotoxicant than fluconazole in vivo in rats.
    Matched MeSH terms: Itraconazole/administration & dosage; Itraconazole/toxicity*
  20. 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
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