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31.
Ina Scholz Heike Oberwittler Klaus-Dieter Riedel Jürgen Burhenne Johanna Weiss Walter E Haefeli Gerd Mikus 《British journal of clinical pharmacology》2009,68(6):906-915
AIMS
The aim was to determine the pharmacokinetics of voriconazole after a single oral dose in comparison with intravenous (i.v.) administration in healthy individuals stratified according to the cytochrome P450 (CYP) 2C19 genotype. In addition, the possible metabolic pathways and their modulation according to CYP2C19 genotype were investigated after oral and i.v. administration of voriconazole.METHODS
In a single-centre, open-label, two-period crossover study 20 participants received single doses of 400 mg voriconazole orally and 400 mg voriconazole intravenously in randomized order. Blood and urine samples were collected up to 96 h post dose and the voriconazole and three major metabolites were quantified by high-performance liquid chromatography coupled to mass spectroscopy.RESULTS
Absolute oral bioavailability of voriconazole was 82.6% (74.1, 91.0). It ranged from 94.4% (78.8, 109.9) in CYP2C19 poor metabolizers to 75.2% (62.9, 87.4) in extensive metabolizers. In contrast to voriconazole and its N-oxide, the plasma concentrations of both hydroxylated metabolites showed a large second peak after 24 h. Independent of the route of administration, voriconazole partial metabolic hydroxylation after i.v. administration was eightfold higher compared with N-oxidation [48.8 ml min−1 (30.5, 67.1) vs. 6.1 ml min−1 (4.1, 8.0)]. The formation of the metabolites was related to CYP2C19 activity.CONCLUSIONS
Independent of the route of administration, voriconazole exposure was three times higher in CYP2C19 poor metabolizers compared with extensive metabolizers. Voriconazole has a high bioavailability with no large differences between the CYP2C19 genotypes. The hydroxylation pathway of voriconazole elimination exceeded the N-oxidation, both influenced by the CYP2C19 genotype. 相似文献32.
In vitro susceptibility of the seven Malassezia species to ketoconazole, voriconazole, itraconazole and terbinafine 总被引:8,自引:0,他引:8
Gupta AK Kohli Y Li A Faergemann J Summerbell RC 《The British journal of dermatology》2000,142(4):758-765
Fifty-five strains, either authentic or ex-type, of seven Malassezia species were investigated for in vitro susceptibility to various concentrations (0.03-64.0 microg/mL) of three azole drugs, ketoconazole, voriconazole and itraconazole, as well as the allylamine terbinafine, using the agar dilution method. All strains of the seven Malassezia species were susceptible to the three azole drugs at low concentrations. M. furfur, M. sympodialis, M. slooffiae, M. pachydermatis, M. globosa, M. obtusa and M. restricta were most sensitive to ketoconazole and itraconazole, with minimum inhibitory concentrations (MICs) ranging from < or = 0.03 to 0.125 microg/mL. The recently introduced antifungal, voriconazole, was also very effective, with MIC80 values < or = 0.03 microg/mL for 80% of strains. MICs of terbinafine against the seven Malassezia species ranged from = 0.03 to 64.0 microg/mL. There were variations in susceptibility of the seven Malassezia species to ketoconazole, voriconazole, itraconazole and terbinafine. Strains of M. furfur, M. globosa and M. obtusa were more tolerant to terbinafine than the remaining Malassezia species; M. sympodialis was highly susceptible. M. furfur strains tested with terbinafine ranged from highly susceptible to relatively resistant. Correct identification of Malassezia species could facilitate selection of appropriate antifungal therapy. 相似文献
33.
34.
W. Shang MD G. Feng MD PhD R. Sun MD X. Wang MD W. Liu MD S. Zhang MD J. Li MD PhD X. Pang MD PhD Y. Wang MD W. Zhang MD PhD 《Journal of clinical pharmacy and therapeutics》2012,37(6):652-656
What is known and Objective: Invasive fungal infections are a major threat to renal transplant recipients. Micafungin and voriconazole are two useful antifungal agents for treating such infections. Our objective is to evaluate the comparative efficacy and safety of micafungin and voriconazole in the initial treatment of such infections. Methods: In this prospective, multicentre, open‐labelled, randomized, controlled trial, renal transplant recipients with invasive fungal infections were assigned to receive either micafungin or voriconazole. The enrolled subjects received a kidney transplant between March 2008 and March 2010 at one of the two transplant centres in Henan Province, China. The efficacy and adverse effects of the two treatments were compared. Results and Discussion: The clinical trial enrolled 65 patients, of whom 31 were treated with micafungin, and 34 with voriconazole. The rates of microbiological evidence of infection in the micafungin and voriconazole groups were 64·5% and 70·5%, respectively, whereas the rates of Candida as the major cultured fungus were 80·0% and 75·0%, respectively. Complicated bacterial infection rates in the two treatment groups were 38·7% and 32·4%, respectively, whereas complicated CMV viral infection occurred at a rate of 19·2% and 23·5%, respectively. Fungal infection within one to 3 months after transplant was 83·6% (26/31) and 85·3% (29/34) in the micafungin and voriconazole groups, respectively. There was no significant difference between the two groups in terms of efficacy, survival beyond 10 days and discontinuation of treatment because of lack of efficacy (P > 0·05). Mortality rates in the micafungin and voriconazole groups were 9·7% (3/31) and 12·1% (4/33), respectively. Rates of adverse effects in the two groups were 41·9% and 51·6% (P > 0·05), respectively. What is new and Conclusions: This is the first comparison of micafungin and voriconazole in renal transplant patients. Our study shows that the effectiveness of micafungin was similar to that of voriconazole in such patients. 相似文献
35.
Candida parapsilosis former groups II and III have recently been established as independent species, named Candida orthopsilosis and Candida metapsilosis, respectively. We investigated the distribution of C. parapsilosis complex species in 122 isolates from blood and other sources in a southern Spain tertiary-care hospital, and we examined the relationship between species, site of isolation and biofilm positivity. We also evaluated the planktonic MICs and sessile MICs (SMICs) of voriconazole, amphotericin B and anidulafungin. One hundred and eleven isolates (91%) were categorized as C. parapsilosis sensu stricto, whereas ten isolates (8.2%) were categorized as C. orthopsilosis and one (0.8%) as C. metapsilosis. Biofilm positivity was observed in 58.5% (65 of 111) of C. parapsilosis sensu stricto isolates vs. 0% (0 of 11) of C. orthopsilosis and C. metapsilosis isolates (p <0.01). There was no difference in biofilm production among C. parapsilosis sensu stricto isolates from blood and other sources. MIC values showed that all isolates were susceptible to voriconazole and amphotericin B, whereas two isolates (1.8%) of C. parapsilosis sensu stricto were non-susceptible to anidulafungin. However, the MIC90 value of voriconazole was higher (0.125 mg/L) for C. orthopsilosis than for C. parapsilosis sensu stricto (0.03 mg/L). In contrast to planktonic cells, the SMICs show that amphotericin B and anidulafungin are moderately effective against the biofilm of C. parapsilosis sensu stricto, whereas voriconazole is ineffective. 相似文献
36.
目的:探讨初诊急性白血病患者化疗期间应用伏立康唑进行预防侵袭性真菌病(IFD)的临床疗效及安全性。方法:回顾性分析2016年02月至2018年03月期间我院血液科收治的初诊急性白血病行化疗的患者166例,按照是否使用抗真菌药进行预防性治疗分为观察组(应用伏立康唑进行预防治疗,n=103)和对照组(未应用抗真菌药物,n=63),比较两组患者IFD发生率差异,并分析抗真菌药物应用的不良反应。结果:观察组IFD发生率为10.7%,对照组为33.3%,两组患者的IFD发生率有明显差异(P<0.05);所有应用伏立康唑进行预防治疗的患者均未出现严重的不良反应。结论:伏立康唑可以有效减低急性白血病患者化疗期间IFD发生率,并且有着较好的安全性,值得在临床推广应用。 相似文献
37.
Luis Octavio Sánchez Vargas Elena Eraso Alfonso Javier Carrillo‐Muñoz José Manuel Aguirre Luis Alberto Gaitán‐Cepeda Guillermo Quindós 《Mycoses》2010,53(3):200-203
Oral candidiasis is the most prevalent complication in HIV‐infected and AIDS patients. Topical antifungal treatment is useful for the initial episodes of oral candidiasis, but most patients suffer more than one episode and fluconazole or itraconazole can help in the management, and voriconazole may represent a useful alternative agent for the treatment of recalcitrant oral and oesophageal candidiasis. The aim of this research was to study the in vitro activity of voriconazole and fluconazole against Mexican oral isolates of clinically relevant yeast. The in vitro susceptibility of 187 oral yeast isolates from HIV‐infected and healthy Mexicans was determined for fluconazole and voriconazole by the M44‐A disc diffusion method. At 24 h, fluconazole was active against 179 of 187 isolates (95.7 %). Moreover, a 100% susceptibility to voriconazole was observed. Voriconazole and fluconazole are highly active in vitro against oral yeast isolates. This study provides baseline data on susceptibilities to both antifungal agents in Mexico. 相似文献
38.
V. Chaitanya B. Sangeetha Lakshmi A.C. Venkata Kumar M. Hari Krishna Reddy R. Ram V. Siva Kumar 《Transplant infectious disease》2015,17(4):605-609
Trichosporon species are basidiomycetous yeast‐like anamorphic organisms (Basidiomycota, Hymenomycetes, Tremelloidae, Trichosporonales) that are widely distributed in nature. Trichosporon species colonize the skin and gastrointestinal tract of humans. We present a report of disseminated Trichosporon in a renal allograft recipient. Our patient satisfied the definitions of both “proven invasive trichosporonosis” and “probable pulmonary infection.” Only 2 reports of disseminated Trichosporon infection in renal transplant recipients, to our knowledge, have been published. 相似文献
39.
Treatment for a eumycetoma infection caused by Aspergillus in an immunocompromised host: a case report 下载免费PDF全文
Eumycetoma is a chronic infection of the skin and subcutaneous tissue caused by filamentous fungi, which usually occurs in tropical or subtropical countries. We report a case of an immunocompromised patient presenting with presumed eumycetoma in the United States and his subsequent treatment with voriconazole. The use of voriconazole and liposomal amphotericin B halted the progression and allowed gradual resolution of the infection. The patient will require close monitoring and long‐term therapy with voriconazole to obtain a clinical cure. Voriconazole and liposomal amphotericin B are potential initial treatment options, with long‐term voriconazole maintenance therapy, for an Aspergillus‐induced eumycetoma. 相似文献
40.
Reduction in incidence of invasive fungal infection in patients receiving allogeneic stem cell transplantation using combined diagnostic‐driven approach and itraconazole oral solution 下载免费PDF全文
Roie Tzadok Michael Y. Shapira Allon E. Moses Reuven Or Colin Block Jacob Strahilevitz 《Mycoses》2015,58(12):694-698
Invasive fungal infections are an important cause of morbidity and mortality after allogeneic haematopoietic stem cell transplantation. We evaluated, in our allogeneic stem cell transplant patients, the effect on the incidence of invasive fungal infection during neutropenia of a strategy combining a diagnostic‐driven approach with chemoprophylaxis during higher risk periods of graft vs. host disease and prolonged neutropenia, using itraconazole oral solution with parenteral voriconazole bridging. One hundred and thirty patients admitted for allogeneic stem cell transplantation within two predefined 20 month periods were included in the study. Data for all patients were collected prospectively. Implementation of the protocol resulted in the administration of more prophylactic antifungals to more patients. Following implementation, there was a non‐significant decrease in the overall number of invasive fungal infections (IFI) [11 of 65 patients (17.2%) vs. 4 of 65 patients (6.2%, P = 0.051)], as well as in the occurrence of invasive mould infections [8 of 65 patients (12.5%) vs. 2 of 65 patients (3.1%, P = 0.054)]. Survival rates at three and 6 months were not significantly affected. A combined diagnostic‐driven approach and antifungal prophylaxis with oral itraconazole and an intravenous voriconazole bridging protocol, was associated with a reduced, albeit non‐statistically significant, number of IFI in our medical centre. 相似文献