Antifungal Drugs Voriconazole Research Articles

MPO-ANCA-positive eosinophilic granulomatosis with polyangiitis complicated by alveolar hemorrhage treated with mepolizumab as an induction therapy: Case report.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis preceded by bronchial asthma or allergic sinusitis and accompanied by peripheral blood eosinophilia. Immunosuppressive drugs, such as cyclophosphamide in addition to high-dose glucocorticoids, are recommended for induction of remission in patients with severe EGPA. Although mepolizumab is widely recognized as remission induction therapy in non-fatal/non-organ disabling or relapsed/refractory EGPA, its efficacy and safety in induction of remission for severe cases have been ambiguous. In this context, we report a case of MPO-ANCA-positive severe EGPA in which the patient had a favorable course using mepolizumab as an induction remission therapy. The patient, a 74-year-old man, had MPO-ANCA-positive severe EGPA with alveolar hemorrhage. High-dose glucocorticoids and intravenous cyclophosphamide were started as remission induction therapy. However, after the initiation of intravenous cyclophosphamide, alveolar hemorrhage worsened, and there was development of opportunistic infections, such as aspergillus and cytomegalovirus antigenemia. Treatment with the antifungal drug voriconazole and the antiviral drug ganciclovir was started for opportunistic infection, and the treatment for EGPA was switched from intravenous cyclophosphamide to mepolizumab. As a result, alveolar hemorrhage improved, glucocorticoids were reduced, and the infection also improved. Mepolizumab as remission induction therapy for severe EGPA were thought to be appropriate and effective treatment in this case. However, the efficacy and safety of mepolizumab for this purpose require comprehensive evaluation.

Development and Evaluation of Voriconazole Loaded Transfersomal Gel for Enhanced Antifungal Activity.

The BCS class II antifungal drug voriconazole (VRC) has a broad spectrum of action. Its solubility is still a major problem for formulation scientists despite numerous attempts to improve it. The thin-film hydration technique produced the voriconazoleloaded Transfersomes, optimized using the Central Composite Design (CCD) and then included as a gel into Poloxamer 407P. Several parameters were assessed for the prepared VRCT, including particle size, zeta potential, surface shape, potential chemical interaction, and polydispersity index (PI). The SEM study also revealed the appearance and surface of optimized transferosomes are symmetrical. The optimized formulation’s average size was found to be 238.8 nm by the particle size analysis. Similarly, a value of 0.449 was found by the polydispersity index (PI). To evaluate voriconazole Transfersomal gel’s (TG4) antibacterial efficacy, an antimicrobial investigation was conducted. The creation of Transfersomal gel formulation offers a topical drug administration method that is more effective and improves patient compliance.

Skin Cancer Induction by the Antimycotic Drug Voriconazole Is Caused by Impaired DNA Damage Detection Due to Chromatin Compaction

Phototoxicity and skin cancer are severe adverse effects of the anti-fungal drug voriconazole (VOR). These adverse effects resemble those seen in xeroderma pigmentosum, caused by defective DNA nucleotide excision repair (NER), and we show that VOR decreases NER capacity. We show that VOR treatment does not perturb the expression of NER, or other DNA damage-related genes, but that VOR localizes to heterochromatin, in complexes containing histone acetyltransferase general control of amino-acid synthesis 5-like 2. Impairment of general control of amino-acid synthesis 5-like 2 binding to histone H3 reduced acetylation of H3, restricting damage-dependent chromatin unfolding, thereby reducing NER initiation. Restoration of H3 histone acetylation using histone deacetylase inhibitors, rescued VOR-induced NER repression, thus offering a preventive therapeutic option. These findings underline the importance of DNA damage-dependent chromatin remodeling as an important prerequisite of functional DNA repair.

Ultrasonic Preparation of Nano-CaCO3 Templates and Hollow Mesoporous SiO2 Nanoparticles for Voriconazole Loading

CaCO3 nanoparticles (nano-CaCO3) as nano-templates were prepared using CaCl2 and Na2CO3 solutions under controlled sonication (19.5 kHz). Using the same ultrasonic device, subsequently, hollow mesoporous silica nanoparticles (HMSNs) were obtained by the hard template of nano-CaCO3. HMSNs were selected as carriers for the antifungal drug voriconazole (VOR) loading to overcome poor water solubility. Three-dimensional CaCO3 nanosheets HMSNs were obtained under gentle sonication. Three-dimensional CaCO3 nanosheets of 24.5 nm (hydrodynamic diameter) were obtained under 17.6 W for 3 min. HMSNs were synthesized by double-template method with nano-CaCO3 as the hard template. Transmission electron microscopy measurements showed that the prepared HMSNs possess hollow structures with particle size between 110 and 120 nm. Nitrogen physisorption at -196 °C revealed that the HMSNs had high surface area (401.57 m2/g), high pore volume (0.11 cm3/g), and uniform pore size (2.22 nm) that facilitated the effective encapsulation of VOR in the HMSNs. The loading capacity of VOR (wt%) on the HMSNs was 7.96%, and the total VOR release amount of VOR-HMSNs material was 71.40% at 480 min. The kinetic model confirmed that the release mechanism of HMSNs nanoparticles followed Fickian diffusion at pH = 7.4 and 37 °C. Moreover, the cumulative VOR release at 42 °C (86.05%) was higher than that at 37 °C (71.40%). The cumulative release amount of VOR from the VOR-HMSNs material was 92.37% at pH = 5.8 at the same temperature. Both nano-CaCO3 templates and HMSNs were prepared by sonication at 19.5 kHz. The as-prepared HMSNs can effectively encapsulate VOR and released drug by Fickian diffusion.Graphical Nano-CaCO3 Templates and Hollow Mesoporous SiO2 Nanoparticles

Design, Development and Optimization of Solid Lipid Nanoparticles for Ocular Delivery of an Antifungal Agent

Oral and intravenous dosing of the second-generation antifungal drug voriconazole (VCZ), with its wide range of antifungal action, is commercially accessible. Visual and hepatic problems might occur when VCZ is used in large doses. Voriconazole SLNs were prepared in this study with the goal of increasing corneal penetration and drug release. The thin fi lm hydration approach was used to make VCZ SLNs. The central composite experimental design was used to maximize the impacts of independent processing factors on vesicle size (R1), drug entrapment effi ciency (%EE) and zeta potential (ZP; R3) responses on lipid concentration (X1), surfactant concentration (X2), and sonication duration (X3). An evaluation of the drug release profi le, corneal penetration, antifungal susceptibility, and cytotoxicity of the improved formula was conducted. The improved recipe achieved the best results with a ZP of -39.6 ± 0.28 mV, an average particle size of 156 ± 3.84 nm, and an EE% of 89.2 ± 2.01. When compared to the unformulated drug solution, the VCZ-SLNs had a prolonged 10 hours drug release profi le with improved corneal penetration, with Papp and Jss measuring 14.35×10-2 cm h-1 and 4.61 mol h-1, respectively, instead of 7.28×10-2 cm h-1 and 2.48 mol h-1. Non-irritating VCZ-SLNs were determined to be corneal tissue, according to the study. Improved corneal penetration and higher antifungal activity without harmful eff ects on ocular tissues were achieved by VCZ-SLNs

Temperature-responsive spin column for sample preparation using an all-aqueous eluent

We present a temperature-responsive spin column using an all-aqueous eluent. The method is intended as a simple sample preparation method for protein removal from serum, which is required for serum drug analysis. As packing materials for the spin column, we prepared two types of silica beads via surface-initiated radical polymerization. The large beads (diameter, 40–63 μm) were grafted with a temperature-responsive cationic copolymer, poly(N-isopropylacrylamide-co-N,N-dimethylaminopropyl acrylamide-co-n-butyl methacrylate) (P(NIPAAm-co-DMAPAAm-co-BMA)), and the small beads (diameter, 5 μm) were grafted with a temperature-responsive hydrophobic copolymer, P(NIPAAm-co-BMA). The beads were packed into the spin column as a double layer: P(NIPAAm-co-BMA) silica beads on the bottom and P(NIPAAm-co-DMAPAAm-co-BMA) silica beads on the top. The sample purification efficacy of the prepared spin column was evaluated on a model sample analyte (the antifungal drug voriconazole mixed with blood serum proteins). At 40 °C, the serum proteins and voriconazole were adsorbed on the prepared spin column via hydrophobic and electrostatic interactions. When the temperature was decreased to 4 °C, the adsorbed voriconazole was eluted from the column with the pure water eluent, while the serum proteins remained in the column. This temperature-responsive spin column realizes sample preparation simply by changing the temperature.

Polymer microparticles with a cavity designed for transarterial chemo-embolization with crystalline drug formulations.

Transarterial chemo-embolization with drug-eluting embolic beads (DEB-TACE) is still evolving. Recent developments include the introduction of radiopaque (X-ray imageable) drug-eluting particles. Here, we report on conceptually different radiopaque polymeric drug-eluting embolic particles, which are (i), cross-linked poly(methacrylates); (ii), radiopaque; (iii), microporous. Furthermore, the particles are not perfectly spherical: they have a large indentation in the sense that they are either a spherical/cup-shaped or ellipsoid/mouth-shaped. The micropores and the large indentation can confer useful features upon the particles, since they can be filled with a crystalline lipophilic chemotherapeutic drug. It is important, in this respect that (i), many potent chemotherapeutics are lipophilic and crystalline; (ii), available drug-eluting beads (DEBs) have the limitation that they can only be used in combination with water-soluble chemotherapeutic agents. Cup- and mouth-shaped particles were obtained in a Cu(0) catalyzed free-radical polymerization reaction. The microparticles could be charged with crystalline drug, in such a manner that the crystals reside in both the micropores and the large cavity, and in quantities that would be required for effective local chemotherapy. The antifungal drug voriconazole, lipophilic, and crystalline, was used to demonstrate this. We believe that the ability of the microporous/cavitated DEBs to carry lipophilic chemotherapeutic drugs is especially important. DEB-TACE is likely to become a cornerstone method of interventional oncology in the years ahead, and the new embolic particles described herein hold the promise of becoming scope widening for the technique.

348 A case of phaeohyphomycosis caused by Corynespora cassiicola, a plant pathogen

Corynespora cassiicola is a common plant pathogen. Humans infected by C. cassiicola are extremely rare. We report a case of subcutaneous and pulmonary phaeohyphomycosis caused by C. cassiicola in a 68-year-old male Chinese. The clinical manifestations were ulcers on the upper arm skin with erosions, scabs, and infiltrative plaques. The pulmonary manifestations presented with cough, chest tightness, and fever. The organism was identified as C. cassiicola based on the morphology and the sequence of the internal transcribed spacer region of the ribosomal RNA gene. CARD9 deficiency has been reported to underlie several fungal infections. By employing whole-exome capture, compound heterozygous sequence variants were found in the CARD9 gene, c.106C>T (p.Gln36*) and c.1118G>C (p.Arg373Pro). The patient was cured by the antifungal drug voriconazole, based on repeated fungal microscopy and culture which were negative. The skin lesions gradually healed, leaving scar and erosive surface. There are less than 10 reports on subcutaneous infection by C. cassiicola, and this case is unique with concomitant subcutaneous and pulmonary phaeohyphomycosis highlighting the role of CARD9 in the human immune response in controlling fungal infections. In summary, this case emphasizes the importance of genetic susceptibility to certain microbial infections.

Efficacy of Voriconazole against Aspergillus fumigatus Infection Depends on Host Immune Function.

Antifungal therapy can fail in a remarkable number of patients with invasive fungal disease, resulting in significant morbidity worldwide. A major contributor to this failure is that while these drugs have high potency in vitro, we do not fully understand how they work inside infected hosts. Here, we used a transparent larval zebrafish model of Aspergillus fumigatus infection amenable to real-time imaging of invasive disease as an in vivo intermediate vertebrate model to investigate the efficacy and mechanism of the antifungal drug voriconazole. We found that the ability of voriconazole to protect against A. fumigatus infection depends on host innate immune cells and, specifically, on the presence of macrophages. While voriconazole inhibits fungal spore germination and growth in vitro, it does not do so in larval zebrafish. Instead, live imaging of whole, intact larvae over a multiday course of infection revealed that macrophages slow down initial fungal growth, allowing voriconazole time to target and kill A. fumigatus hyphae postgermination. These findings shed light on how antifungal drugs such as voriconazole may synergize with the immune response in living hosts.

In Vitro Efficacy of Chlorhexidine and a riboflavin/UVA Combination on Fungal Agents of Keratitis

ABSTRACT Purpose Mycotic keratitis is a global ophthalmological problem because it is difficult to diagnose and treat. The aim of the current study was to evaluate the efficiency of using antifungal agents amphotericin B (AMB), voriconazole (VRC), 0.02% chlorhexidine (CHX), and a combination of riboflavin and UVA treatment against two fungal genera (Aspergillus and Fusarium) responsible for keratitis. Methods We evaluated antifungal efficiencies of riboflavin/UVA and the antifungal drugs VRC, AMB, and CHX (alone and in combination) against fungal inocula at four concentrations. We recorded colony counts of isolates for Aspergillus terreus, A. flavus, A. fumigatus, Fusarium falciforme, F. proliferatum, and F. solani on Mueller-Hinton agar plates. Results Fungal suspensions exposed to the following treatment combinations did not allow fungal growth: riboflavin/UVA and VRC, riboflavin/UVA and AMB, riboflavin/UVA and CHX, and CHX alone. We observed a statistically significant reduction (P < .05) in the number of colonies on agar plates when fungal suspensions were treated with riboflavin/UVA, VRC, and AMB only. Conclusions Riboflavin/UVA treatment in combination with AMB, VRC, and CHX are capable of killing keratitis-inducing fungi (P < .05). The antiseptic CHX exerted a considerable antifungal effect on all strains we examined. Therefore, we recommend CHX as additional therapy against mycotic keratitis, particularly when keratitis is caused by multi-resistant members of Fusarium.

Effects of ketoconazole, voriconazole, and itraconazole on the pharmacokinetics of apatinib in rats

We investigated the effect of azole antifungal drugs (ketoconazole, voriconazole, and itraconazole) on the pharmacokinetics of apatinib in rats. The rats in ketoconazole, voriconazole, and itraconazole groups received single-dose apatinib 30 mg/kg after the oral administration of ketoconazole, voriconazole, and itraconazole, respectively. Co-administration of ketoconazole or voriconazole significantly increased the apatinib Cmax and AUC(0–t) and decreased the clearance. Co-administration of itraconazole did not significantly affect the pharmacokinetics parameters of apatinib. It could be concluded that both ketoconazole and voriconazole significantly increase the exposure of apatinib, and affect the pharmacokinetics of apatinib in rat. Apatinib can be co-administered with itraconazole, but ketoconazole and voriconazole should be avoided if possible or be underwent therapeutic drug monitoring of apatinib. A further clinical study should be conducted to investigate the inhibitory effect of azole antifungal drugs on the apatinib plasma concentration.

Manual punch versus automated flow-through sample desorption for dried blood spot LC-MS/MS analysis of voriconazole

Dried blood spot (DBS) sampling is a patient-friendly alternative for plasma sampling for the purpose of therapeutic drug monitoring (TDM). To speed up the analysis time, an automated flow-through desorption method of DBS samples may be beneficial. This article describes the cross-validation of a manual punch DBS method with an automated desorption (DBS autosampler, DBSA) method for the DBS analysis of the antifungal drug voriconazole, followed by cross-validation of both DBS methods with a plasma-based method, and an assessment of agreement between DBS/DBSA and regular plasma concentration measurements (gold standard) in samples from patients on voriconazole treatment.DBS and DBSA LC-MS/MS assays for voriconazole were validated according to the latest guidelines on bioanalytical method validation (FDA, EMA). Additional DBS-specific validation parameters included hematocrit effect and the influence of spot volume. Passing-Bablok regression and Bland-Altman plots were used to cross-validate the punch DBS, DBSA and plasma methods. The assessment of agreement between DBS/DBSA and plasma concentration measurements involved the performance of DBS/DBSA measurements to predict voriconazole plasma concentrations in patient samples.Both DBS methods complied with all validation parameters. Sample pre-processing time was reduced from 1.5 h to 3 min when using the DBSA. Cross-validation of both DBS methods showed a proportional bias and a correction factor was needed to interchange voriconazole concentrations of both DBS methods. Similarly, the punch DBS method required a factor to correct for proportional bias compared to the plasma method, but the DBSA and plasma assays showed no bias. Limits of agreement of the DBS/DBSA and plasma assays in Bland-Altman analysis were relatively wide, i.e. 0.75–1.28 for the DBS punch method versus plasma method and 0.57–1.38 for the DBSA versus plasma assay. Interpretation of DBS, DBSA and plasma samples in terms of concentrations in or outside of the voriconazole therapeutic range agreed in 82–86% of the cases.The variability in paired DBS/DBSA and plasma concentration measurements is considered high for TDM purposes and this limitation should be balanced against the advantages of DBS sampling of voriconazole and the speed of flow through desorption.

Molecular and cellular responses of the pathogenic fungus Lomentospora prolificans to the antifungal drug voriconazole.

The filamentous fungus Lomentospora (Scedosporium) prolificans is an emerging opportunistic pathogen associated with fatal infections in patients with disturbed immune function. Unfortunately, conventional therapies are hardly of any use against this fungus due to its intrinsic resistance. Therefore, we performed an integrated study of the L. prolificans responses to the first option to treat these mycoses, namely voriconazole, with the aim of unveiling mechanisms involved in the resistance to this compound. To do that, we used a wide range of techniques, including fluorescence and electron microscopy to study morphological alterations, ion chromatography to measure changes in cell-wall carbohydrate composition, and proteomics-based techniques to identify the proteins differentially expressed under the presence of the drug. Significantly, we showed drastic changes occurring in cell shape after voriconazole exposure, L. prolificans hyphae being shorter and wider than under control conditions. Interestingly, we proved that the architecture and carbohydrate composition of the cell wall had been modified in the presence of the drug. Specifically, L. prolificans constructed a more complex organelle with a higher presence of glucans and mannans. In addition to this, we identified several differentially expressed proteins, including Srp1 and heat shock protein 70 (Hsp70), as the most overexpressed under voriconazole-induced stress conditions. The mechanisms described in this study, which may be directly related to L. prolificans antifungal resistance or tolerance, could be used as targets to improve existing therapies or to develop new ones in order to successfully eliminate these mycoses.

Pulmonary Delivery of Voriconazole Loaded Nanoparticles Providing a Prolonged Drug Level in Lungs: A Promise for Treating Fungal Infection.

Current therapies are insufficient to prevent recurrent fungal infection especially in the lower part of the lung. A careful and systematic understanding of the properties of nanoparticles plays a significant role in the design, development, optimization, and in vivo performances of the nanoparticles. In the present study, PLGA nanoparticles containing the antifungal drug voriconazole was prepared and two best formulations were selected for further characterization and in vivo studies. The nanoparticles and the free drug were radiolabeled with technetium-99m with 90% labeling efficiency, and the radiolabeled particles were administered to investigate the effect on their blood clearance, biodistribution, and in vivo gamma imaging. In vivo deposition of the drug in the lobes of the lung was studied by LC-MS/MS study. The particles were found to be spherical and had an average hydrodynamic diameter of 300 nm with a smooth surface. The radiolabeled particles and the free drug were found to accumulate in various major organs. Drug accumulation was more pronounced in the lung in the case of administration of the nanoparticles than that of the free drug. The free drug was found to be excreted more rapidly than the nanoparticle containing drug following the inhalation route as assessed by gamma scintigraphy study. Thus, the study reveals that pulmonary administration of nanoparticles containing voriconazole could be a better therapeutic choice even as compared to the iv route of administration of the free drug and/or the drug loaded nanoparticles.

In Vitro Activity of Calcium Sulfate and Hydroxyapatite Antifungal Disks Loaded with Amphotericin B or Voriconazole in Consideration for Adjunctive Osteomyelitis Management.

Background: Regarding antibiotic-loaded cements, there is an abundant amount of literature regarding the antibacterial in vitro inhibitory and clinical applications for the treatment of osteomyelitis. The opposite can be said about literature regarding in vitro antifungal-loaded cement drug delivery for the treatment of fungal osteomyelitis. Methods: Aspergillus fumigatus and Candida (ATCC 10231; ATCC, Manassas, Virginia) were plated on antibiotic/antifungal-free plates. Voriconazole- and amphotericin B-impregnated calcium sulfate and hydroxyapatite (HA) disks, calcium sulfate + HA control disks, and control polymethylmethacrylate disks were laid separately onto plates separately inoculated with Aspergillus and Candida spp. The zones of inhibition obtained were measured in millimeters at 24, 36, and 96 hours. Results: Etest (bioMérieux, Marcy l'Etoile, France) results demonstrated susceptibility of Aspergillus and Candida to amphotericin B and voriconazole. The zone of inhibition data demonstrated that voriconazole and amphotericin B retained their antifungal activity when mixed into the calcium sulfate + HA bone void filler and eluted at biologically effective antifungal concentrations over 96 hours. Conclusions: The calcium sulfate + HA bone void filler is a biocompatible ceramic carrier vehicle that can successfully deliver the antifungal drugs voriconazole and amphotericin B in the adjunctive treatment of fungal osteomyelitis. It is a reliable strategy in the local delivery of antifungal drugs to an area of osteomyelitis.

In vitro activity of calcium sulfate and hydroxyapatite antifungal disks loaded with amphotericin B or voriconazole in consideration for adjunctive osteomyelitis management.

Regarding antibiotic-loaded cements, there is an abundant amount of literature regarding the antibacterial in vitro inhibitory and clinical applications for the treatment of osteomyelitis. The opposite can be said about literature regarding in vitro antifungal-loaded cement drug delivery for the treatment of fungal osteomyelitis. Aspergillus fumigatus and Candida (ATCC 1023ATCC, Manassas, Virginia) were plated on antibiotic/antifungal-free plates. Voriconazole- and amphotericin B-impregnated calcium sulfate and hydroxyapatite (HA) disks, calcium sulfate + HA control disks, and control polymethylmethacrylate disks were laid separately onto plates separately inoculated with Aspergillus and Candida spp. The zones of inhibition obtained were measured in millimeters at 24, 36, and 96 hours. Etest (bioMérieux, Marcy l'Etoile, France) results demonstrated susceptibility of Aspergillus and Candida to amphotericin B and voriconazole. The zone of inhibition data demonstrated that voriconazole and amphotericin B retained their antifungal activity when mixed into the calcium sulfate + HA bone void filler and eluted at biologically effective antifungal concentrations over 96 hours. The calcium sulfate + HA bone void filler is a biocompatible ceramic carrier vehicle that can successfully deliver the antifungal drugs voriconazole and amphotericin B in the adjunctive treatment of fungal osteomyelitis. It is a reliable strategy in the local delivery of antifungal drugs to an area of osteomyelitis.

Acute effect of Fluconazole, Itraconazole and Voriconazole on blood glucose in normoglyceamic &amp; diabetic rats: an experimental study

Anti-fungal and antimicrobials are frequently co-prescribed either to manage or treat either the secondary complications or other diseases. Among antifungal drugs Fluconazole, Itraconazole & Voriconazole are most commonly used. The present study was undertaken to further confirm the effect of Voriconazole as well as other antifungal drugs on blood Glucose level. Aim & Objectives: 1. To Study the effect of Fluconazole, Itraconazole & Voriaconazole in Normoglycemic & Diabetic Rats on Blood Glucose. 2. To compare the effects between all drugs. Material & Methodology: Grouping: Animals divided into 8 groups in each group 6 animals. Group 1- 4: Normoglycemic rats, Group 5-8 Diabetic rats (alloxan induced) Group 1,5: received vehicle (Normal saline) Group 2,6: received Fluconazole (18mg/kg BW), Group 3,7 received Itraconazole (18mg/kg BW) Group 4,8 received Voriconazole (18mg/kg BW). The glucose levels were estimated by Glucometer method (Accu-check active) at the interval of 0, ½ hr, 1hrs, 2hrs & 4hrs after drug administration. Results: Effect on blood glucose in Normoglycemic Rats: Voriconazole had a significant hypoglycaemic effect which appeared after 1 hr (‘p’ value= 0.0102) of administration & persisted up to 2 hrs (‘p’ value=0.0001). However effect of Voriconzole was found to be declined after 2 hrs. There was no significant change in blood glucose in normoglycemic rats with Fluconazole & Itraconazole. Effect on blood glucose in Diabetic Rats: (Table 2): Voriconazole had a significant hypoglycaemic effect which appeared after 1 hr (‘p’ value=0.013) of administration & persisted up to 2 hrs (‘p’ value=0.001) in acute studies. However effect of Voriconzole was found to be declined after 2 hrs. There was no significant change in blood glucose in diabetic rats with Fluconazole & Itraconazole treated. Conclusion: Itraconazole, Fluconazole can be safely used in diabetic with fungal infections. Voriconazole should be avoided in diabetics to minimise the further hypoglycaemia.

Synthesis of Isomeric and Potent Impurities of the Triazole-Based Antifungal Drug Voriconazole.

We describe the synthesis of two positional isomers and a desfluoro impurity of Voriconazole starting with Friedel–Crafts acylation of mono- and difluorobenzene. These isomers are the crucial components in determining the quality of Voriconazole during its manufacturing from the key raw material, 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one. All the prepared impurities were characterized by IR, 1H-NMR, 13C-NMR, and mass spectral data.

Transplant antifungal drug voriconazole associated with increased skin cancer risk

Transplant antifungal drug voriconazole associated with increased skin cancer risk

Quantification of Antifungal Drug Voriconazole in Serum and Plasma by HPLC-UV

A simple, sensitive and rapid high-performance liquid chromatographic (HPLC) method for the determination of voriconazole in human serum or plasma was developed. Voriconazole and internal standard clonazepam were extracted from plasma or serum with methanol and analyzed on a Microsorb-MV C18 column with ultraviolet (UV) detection set at wavelengths of 256 and 310 nm, respectively. The calibration curve was linear through the range of 0.1-10 mg/L using a 0.1 mL sample volume. The within-run and between-run precisions were all less than 6%. Accuracies ranged from 97 to 106%. Absolute recovery was 96.4 ± 1.3% for voriconazole. The method has been applied to monitor voriconazole use in order to ascertain clinical efficacy and minimize toxic effects.