Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new voriconazole research articles will be listed here shortly after becoming available to us.
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Medical research on voriconazole
Voriconazole in the treatment of fungal eye infections: a review of current literature.
Br J Ophthalmol. 2008 Jul; 92(7): 871-8
Hariprasad SM, Mieler WF, Lin TK, Sponsel WE, Graybill JR
BACKGROUND: Voriconazole has an important role to play in the prophylaxis and management of fungal endophthalmitis and keratitis. New-generation triazoles, including voriconazole, posaconazole and ravuconazole, have been shown in laboratory studies and clinical experience to have very good safety profiles with few side effects. Fungal eye infections, while not common in temperate climates, have been notoriously difficult to diagnose and treat, and generally result in protracted therapy with poor final outcomes. Current treatment options are far from optimal. AIMS: This paper will review studies and clinical case reports published in the ophthalmic literature that address the safety of these drugs in the eye, penetration and concentration in ocular tissues and media, and efficacy in treating common pathogens implicated in fungal keratitis and endophthalmitis. CONCLUSIONS: Over 40 clinical case reports of treatment with voriconazole suggest that it may be used safely and effectively against a broad range of fungal pathogens.
Visual disturbance comorbid with hallucination caused by voriconazole in the Japanese population.
Int J Hematol. 2008 Jun 24;
Imataki O, Ohnishi H, Kitanaka A, Kubota Y, Ishida T, Tanaka T
Voriconazole (VRCZ) has a curious visual adverse event that is completely reversible, but its mechanism has not been fully addressed. We observed 20 consecutive patients treated with VRCZ after chemotherapy for hematological malignancy. Six of these cases experienced visual disturbance, and all cases among those treated with oral VRCZ. The authors discuss a relatively higher frequency of visual events complicated with hallucination, which might be associated with a special metabolism of VRCZ in Japanese patients with hematological malignancies. Hallucination and oral administration were specific clinical features for the patients presenting with visual adverse events in response to VRCZ.
Antifungal activity of 25-azalanosterol against Candida species.
Eur J Clin Microbiol Infect Dis. 2008 Jun 24;
Wang J, Wu J
The antifungal properties of 25-azalanosterol was investigated. Compared to normal antifungal reagents, fluoconazole, clotrimazole and voriconazole, it exhibited significant anti-Candida activity (the minimum inhibitory concentration [MIC] ranges were 0.125-8, 0.5-8 and 0.5-32 microg/mL against C. albicans, C. krusei and C. glabrata, respectively), but showed little toxicity to mice liver cells at clinical dosage after 24 h of exposure, with the lowest lactate dehydrogenase and the highest ED(50) compared to four other azoles antifungal agents. 25-Azalanosterol inhibited the incorporation of [methyl-(3)H(3)] AdoMet into the C-24 of ergosterol in whole cells of C. albicans. Thus, 25-azalanosterol, as an inhibitor of the growth of C. albicans in vitro, may have considerable potential as a new class of anti-Candida agent that lacks toxic side effects in the mammalian host.
Eur J Clin Microbiol Infect Dis. 2008 Jun 18;
Nomura K, Fujimoto Y, Kanbayashi Y, Ikawa K, Taniwaki M
Voriconazole has been shown to be safe and effective for fungal infection. However, its population pharmacokinetics for patients with hematological malignancies remains unknown. We performed a population pharmacokinetics study of nine hematological patients with 36 points samples. We approximated the drug concentration curve using a linear one-compartment model. The distribution of volume (Vd), elimination rate constant, and clearance (CL) were 68.7 L, 0.163 h(-1), and 11.2 L/h, respectively. By coincidence, our study has verified that the current administration is enough to treat fungus infections by using Monte Carlo simulation. Our data demonstrated that the current administration method is appropriate and effective. Our results may prove to be useful as a basic reference for the clinical usage of voriconazole.
J Clin Microbiol. 2008 Jun 18;
Pfaller MA, Messer SA, Boyken L, Rice C, Tendolkar S, Hollis RJ, Diekema DJ
Few data exist to describe in vitro patterns of cross resistance among large collections of clinical Aspergillus, including species other than A. fumigatus. We examined 771 Aspergillus spp. clinical isolates collected from 2000-2006 as part of a global antifungal surveillance program (553 A. fumigatus, 76 A. flavus, 59 A. niger, 35 A. terreus, 24 A. versicolor, and 24 other Aspergillus species). Antifungal susceptibility testing was performed by the Clinical and Laboratory Standards Institute (CLSI) M38-A broth dilution method against itraconazole( ITR), posaconazole (POS), ravuconazole (RAV) and voriconazole (VOR). We examined the potential for cross-resistance using measures of correlation overall and by species. Most Aspergillus had MICs of 2 microg/mL to VOR or POS remain extremely rare (
Voriconazole-Induced Neuropathy.
Chemotherapy. 2008 Jun 18; 54(3): 224-227
Aksoy F, Akdogan E, Aydin K, Yilmaz M, Altunayoglu V, Sozen EE, Omay SB, Koksal I
Background: Fungal infections are common and life threatening among immunosupressive patients. Rare side effects may occur related to the use of voriconazole, which is the drug of choice in invasive aspergillosis. Patients and Methods: Neuropathy was determined through clinical and electromyographic findings during the course of voriconazole therapy in 2 patients developing invasive aspergillosis. Results: Since examinations revealed no neuropathy capable of ascription to any other cause and improvement followed the cessation of the drug, this suggested that neuropathy may be linked to voriconazole use. Conclusion: Neuropathy may be seen as a side effect during voriconazole treatment. Voriconazole-induced side effects should be borne in mind and patients carefully monitored during its use.
J Antimicrob Chemother. 2008 Jun 10;
Lamaris GA, Ben-Ami R, Lewis RE, Kontoyiannis DP
Objectives Voriconazole and posaconazole are effective as both prophylaxis and treatment for invasive aspergillosis (IA) in immunocompromised patients. Hence, it is important to determine whether Aspergillus pre-exposure to voriconazole or posaconazole diminishes subsequent posaconazole or voriconazole activity, respectively. Methods We used Aspergillus fumigatus (AF) 293 conidia with or without prior exposure to voriconazole or posaconazole [three serial passages on plates containing regular yeast extract-glucose (YAG) media, YAG+0.0625 mg/L voriconazole or YAG+0.025 mg/L posaconazole]. Toll-deficient Drosophila melanogaster flies were infected by injection, and 8 day survival was monitored. Following infection, flies were fed either regular food, food containing 1000 mg/L voriconazole (posaconazole-exposed conidia) or 1000 mg/L posaconazole (voriconazole-exposed conidia). Voriconazole and posaconazole concentrations in flies were confirmed by HPLC. Results AF inoculation resulted in 71% mortality 8 days post-infection (median survival 4 days). Prior conidial exposure to voriconazole or posaconazole did not affect mortality (73%, P = 0.8 for voriconazole pre-exposed and 76%, P = 0.49 for posaconazole pre-exposed). Voriconazole treatment post-infection had a protective effect, reducing mortality to 42% (P = 0.0002), while prior conidial exposure to posaconazole did not alter the protective effect of voriconazole (34% 8 day mortality, P = 0.35). Likewise, posaconazole treatment post-infection reduced mortality to 36%, while prior conidial exposure to voriconazole did not alter the protective effect of posaconazole (39% mortality, P = 0.92). Median fly homogenate concentrations of voriconazole and posaconazole were 0.44 and 2.05 mg/L, respectively. Conclusions Prior exposure of AF to voriconazole or posaconazole did not affect the virulence of AF nor the subsequent activity of the alternate triazole in a Drosophila model of IA.
Clin Drug Investig. 2008; 28(7): 409-20
Abel S, Allan R, Gandelman K, Tomaszewski K, Webb DJ, Wood ND
BACKGROUND AND OBJECTIVES: Since little is known regarding the pharmacokinetics of voriconazole in renally impaired patients, two prospective, open-label, parallel-group volunteer studies were conducted to estimate the effect of renal impairment on the pharmacokinetics of oral voriconazole and intravenous voriconazole solubilized with sulphobutylether-beta-cyclodextrin (SBECD), respectively. METHODS: In study A, male subjects with no (n = 6), mild (n = 6), moderate (n = 6) or severe (n = 6) renal impairment received one 200 mg dose of oral voriconazole. Voriconazole plasma levels were periodically assessed until 48 hours post-dose. In study B, male subjects with no (n = 6) or moderate (n = 7) renal impairment received multiple doses of intravenous voriconazole solubilized with SBECD (6 mg/kg twice daily [day 1] then 3 mg/kg twice daily [days 2-6] followed by a final dose of 3 mg/kg on the morning of day 7) at an infusion rate of 3 mg/kg/h. Voriconazole plasma levels were periodically assessed until 36 hours following the final dose. Pharmacokinetics were determined by non-compartmental methods. RESULTS: The pharmacokinetics of voriconazole were unaffected in subjects with any degree of renal impairment in both studies. In study B, clearance of SBECD was proportional to creatinine clearance (r(2) = 0.857). Although two subjects had >30% increase in serum creatinine from baseline, these changes did not correlate with SBECD trough levels (r(2) = 0.053). The majority of subjects with moderate renal insufficiency were able to tolerate 7 days of intravenous voriconazole solubilized with SBECD. CONCLUSION: These data suggest that renal impairment does not affect the pharmacokinetics of voriconazole. Furthermore, in subjects with moderate renal impairment, there is a strong linear correlation between SBECD clearance and creatinine clearance, and elevated SBECD levels do not necessarily correlate with increased serum creatinine levels (an indicator of worsening renal function).
Endogenous mycotic endophthalmitis in an immunocompetent patient.
Int Ophthalmol. 2008 Jun 5;
Gupta P, Sachdev N, Kaur J, Dey P, Gupta V, Gupta A
Acute and invasive fungal infections are usually seen in immunocompromised and debilitated patients. We report a young immunocompetent 28-year-old Indian male who presented with unilateral endogenous endophthalmitis in the left eye and was managed with pars plana vitreous surgery. The polymerase chain reaction from the vitrectomy specimen tested positive for the fungal genome while the cytology examination identified aseptate hyphae with wide-angle branching, most likely suggesting Zygomycosis. A detailed systemic evaluation failed to reveal any systemic focus or predisposing factor for fungal infection. The patient had received intravenous dextrose infusions while undergoing a surgical procedure for post-traumatic hydrocele elsewhere a week prior to this episode. The patient was successfully managed with pars plana vitreous surgery along with intravitreal Amphotericin-B and oral Voriconazole.
Osteomyelitis of the rib caused by Aspergillus flavus following cardiac surgery.
Mycoses. 2008 Jun 3;
Verghese S, Chellamma T, Cherian KM
Deep sternal wound infections are a rare but severe complication of coronary artery bypass graft (CABG) surgery, with an estimated prevalence of 1%-4%. We report a case of osteomyelitis of the rib and chest wall abscess caused by Aspergillus flavus in a CABG patient, which was treated successfully with voriconazole.