Sporanox scientific update |
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Int J Clin Pharmacol Ther. 2005 Feb;43(2):109-16.
Estevez-Carrizo FE, Ruiz S, Bellocq B, Leal C, Siri MT, del Campo MJ.
Center for Biomedical Sciences, University of Montevideo, Montevideo, Uruguay.
Simultaneous itraconazole bioequivalence assessment and CYP3A phenotyping in South American subjects.
A study on concurrent itraconazole bioequivalence evaluation and CYP3A phenotyping in South American subjects. The study appraises the sensitive outcome of a single-dose itraconazole administration on CYP3A phenotype. Here the author reports the evaluation of the bioequivalence of an itraconazole formulation.
OBJECTIVE: The present study evaluates the acute effect of a single-dose itraconazole administration on CYP3A phenotype, as measured by cortisol MR ratio in urine. METHODS: Twenty-four healthy Uruguayan subjects recruited according to strict inclusion criteria participated in an open-label, randomized, two-period, crossover study designed to evaluate the bioequivalence of an itraconazole formulation (Traconal 100 mg, Ache Labs, Sao Paulo, Brazil). The study comprised two treatment periods separated by a wash-out period of 14 days. In each period a series of venous blood samples were drawn over 48 hours. Three urine samples were obtained for CYP3A phenotyping: pre-dose, 24 and 48 hours after dosing. Blood and urine samples were assayed for itraconazole, beta-hydroxycortisol and cortisol using a validated chromatographic method. RESULTS: The ratio of the mean AUC0-inf. T/AUC0-inf. R was included in the bioequivalence range, however, due to high variability, the CI90% was not. It was found that the cortisol metabolic ratio (MR) showed inhibition relative to basal activity in a proportion of subjects 24 hours (68 +/- 6.1%, mean +/- CI95%) and 48 hours (80 +/- 7.3%, mean +/- CI95%) after ingestion of itraconazole. A significant correlation was found between itraconazole AUC0-inf. and normalized basal CYP3A MR for the reference (r = 0.62, t = 3.72, p = 0.001) and the test product (r = 0.74, t = 5.22, p = 0.00003). A good correlation existed between basal cortisol MR and the elimination half-life of itraconazole. CONCLUSIONS: The findings are in line with the hypothesis that the determination of the bioavailability of highly variable CYP3A substrates might be improved by simultaneous non-interfering phenotyping. If this is confirmed, a new methodological paradigm may need to be developed in order to take account of metabolic variability in bioequivalence evaluation of this group of drugs.
Med Mycol. 2005 Feb;43(1):91-5.
Al-Abdely M, Alkhunaizi AM, Al-Tawfiq JA, Hassounah M, Rinaldi MG, Sutton DA.
Section of Infectious Diseases, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Successful therapy of cerebral phaeohyphomycosis due to Ramichloridium mackenziei with the new triazole posaconazole.
The treatment of cerebral phaeohyphomycosis using new triazole posaconazole. Cerebral phaeohyphomycosis is caused by Ramichloridium mackenziei and is universally fatal. The treatment using posaconazole is best to get a progressive clinical and radiologic improvement.
Cerebral phaeohyphomycosis caused by Ramichloridium mackenziei is universally fatal. All reported cases with long-term follow-up have indicated 100% mortality despite antifungal therapy and surgical intervention. We describe the case of a 62-year-old patient who underwent renal transplantation and had a cerebral abscess caused by R. mackenziei. The infection progressed despite surgical evacuation and therapy with liposomal amphotericin B, itraconazole, and 5-flucytosine. The patient was subsequently treated with the investigational triazole posaconazole oral suspension, 800 mg/day, in divided doses. Treatment with posaconazole resulted in progressive clinical and radiologic improvement. The patient is alive four years after diagnosis and maintained on posaconazole therapy. This case supports the potential role of this extended-spectrum azole in the treatment of this serious fungal infection of the central nervous system.
J Clin Pharm Ther. 2005 Jun;30(3):201-6.
Lohitnavy M, Lohitnavy O, Thangkeattiyanon O, Srichai W.
Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand.
Reduced oral itraconazole bioavailability by antacid suspension.
A study to check the effectiveness of antacid suspension on oral absorption of itraconazole. This randomized, open-labelled, two-period, crossover study was conducted in 12 healthy patients. Co-administration of itraconazole and antacid suspension is not a good method of treatment.
Summary Aims: To investigate the effects of antacid suspension on oral absorption of itraconazole. Methods: A randomized, open-labelled, two-period, crossover study with a 1-week washout period was conducted in 12 healthy Thai male volunteers. The participants were allocated in either treatment A or B in the first period. In treatment A, the volunteers were orally administered with 200 mg of itraconazole alone. In treatment B, the volunteers were administered orally with 200 mg of itraconazole co-administered with antacid suspension. Serial serum samples were collected over the period of 24 h and subsequently analysed by using a validated high-pressure liquid chromatographic method with ultraviolet detection. Pharmacokinetic parameters were determined by non-compartmental analysis. Results: Time to reach maximal concentration (T(max)), maximal concentration (C(max)) and area under the curve (AUC(0--infinity)) were markedly decreased in antacid-treated group. T(max) for treatment A was 3.0 +/- 0.4 and 5.1 +/- 2.7 h for treatment B. C(max) and AUC(0--infinity) of treatments A and B were 146.3 +/- 70.5 vs. 43.6 +/- 16.9 (ng/mL) and 1928.5 +/- 1114.6 vs. 654.8 +/- 452.2 (ng.h/mL) respectively. 90% Confidence interval (90% CI) of C(max) and AUC(0--infinity) were 24.1-42.1 and 16.2-65.9 respectively. Conclusions: Rate and extent of itraconazole oral absorption were markedly decreased by concurrent use of antacid suspension. Hence, co-administration of itraconazole and antacid suspension should be avoided.
Indian J Ophthalmol. 2001 Sep;49(3):173-6.
Agarwal PK, Roy P, Das A, Banerjee A, Maity PK, Banerjee AR.
Regional Institute of Ophthalmology, Medical College, Calcutta, India.
Efficacy of topical and systemic itraconazole as a broad-spectrum antifungal agent in mycotic corneal ulcer. A preliminary study.
A preliminary study on the effectiveness of topical and systemic itraconazole as a broad-spectrum antifungal agent in mycotic corneal ulcer. The study evaluated the effect of itraconazole against common fungi which cause mycotic corneal ulcer. It is found that itraconazole effective in the treatment of mycotic corneal ulcer.
PURPOSE: To evaluate the efficacy of topical (1%) and systemic itraconazole against common fungi such as Aspergillus and other filamentous fungi that cause mycotic corneal ulcer. METHODS: A prospective randomised, controlled study was done in 54 clinically suspected cases of fungal keratitis of which 44 were culture proven. Half the cases (n=27) with superficial involvement were treated with only topical itraconazole (1%) and the other half were treated with both topical and systemic itraconazole. RESULTS: Aspergillus, Penicillium and Fusarium were the most common fungi isolated. The ulcer resolved in 42 eyes (77%) and 12 eyes (23%) did not respond well to treatment. Four of 12 non-responding eyes were caused by Fusarium species. CONCLUSION: Itraconazole, given either topically or systemically, is effective in treating mycotic corneal ulcers.
Diagn Microbiol Infect Dis. 2005 May;52(1):15-20.
Lionakis MS, Lewis RE, Torres HA, Albert ND, Raad II, Kontoyiannis DP.
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Increased frequency of non-fumigatus Aspergillus species in amphotericin B- or triazole-pre-exposed cancer patients with positive cultures for aspergilli.
Augmented incidence of non-fumigatus Aspergillus species with optimistic cultures for aspergilli in amphotericin B- or triazole-pre-exposed cancer patients. In cancer patients with positive Aspergillus cultures have high frequency of non-fumigatus Aspergillus species. These Aspergillus isolates were AMB resistant.
Invasive aspergillosis (IA) can occur despite prior prophylactic or empiric use of triazoles or amphotericin B (AMB). Although profound immunosuppression may account for breakthrough IA, resistance of Aspergillus to antifungals may also play a role. To examine this question, we measured the minimal inhibitory concentration of 105 Aspergillus isolates recovered from 105 cancer patients (64 with IA, 41 with Aspergillus colonization) to AMB, itraconazole (ITC), and voriconazole (VRC) using the National Committee for Clinical Laboratory Standards (NCCLS) M38-A microdilution and E-test methods. We also determined the minimal fungicidal concentration (MFC) of these agents and the minimal effective concentration (MEC) of caspofungin (CAS) using standardized methods. We then collected information regarding pre-exposure to AMB or triazoles (fluconazole, ITC, VRC) within 3 months before Aspergillus isolation. Pre-exposure of cancer patients to AMB or triazoles was associated with increased frequency of non-fumigatus Aspergillus species. Aspergillus isolates recovered from patients who previously received AMB exhibited higher E-test AMB MICs compared with isolates from patients without prior AMB exposure (P = 0.01). In addition, the AMB MICs by E-test were higher in triazole-pre-exposed patients compared with those not exposed to triazoles (P = 0.001). The ITC and VRC MICs by E-test were not affected by prior AMB or triazole exposure. Finally, neither the AMB, ITC, and VRC MICs and MFCs by NCCLS method nor CAS MECs showed such changes. In conclusion, cancer patients with positive Aspergillus cultures who are pre-exposed to AMB or triazoles have high frequency of non-fumigatus Aspergillus species. These Aspergillus isolates were found to be AMB-resistant by the more sensitive E-test method.
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Drug category:Antifungals
 Sporanox scientific update
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