Treatment of invasive fungal infections: stability of voriconazole infusion solutions in PVC bags

Abstract

Voriconazole is a novel broad-spectrum antifungal drug, employed in the treatment of invasive fungal infections, and represents an alternative to amphotericin B treatment. The manufacturer recommends that any unused reconstituted product should be stored at 2 masculineC to 8 masculineC, for no more than 24 h, but no recommendations about i.v. infusion solutions are given. Previous works have reported on the stability of voriconazole in polyolefin bags and just one in 5% dextrose polyvinyl chloride (PVC) bags, at a 4 mg.mL-1 concentration. In this work, the stability of voriconazole as an i.v. infusion solution in 0.9% sodium chloride and in 5% dextrose, in PVC bags, at 0.5 mg.mL-1, stored at 4 masculineC and at room temperature, protected from light, was evaluated. These infusion solutions were analyzed for a 21-day period. Chemical stability was evaluated by HPLC assay. Visual inspection was performed and pH of the solutions was measured. No color change or precipitation in the solutions was observed. The drug content remained above 90% for 11 days in 0.9% sodium chloride and for 9 days in 5% dextrose solutions. The i.v. infusion solutions stored at room temperature were not stable. At room temperature, the voriconazole content dropped down to 88.3 and 86.6%, in 0.9% sodium chloride or 5% dextrose solutions, respectively, two days after admixture. Assays performed at the end of the study suggest the sorption of voriconazole by the PVC bags. The results of this study allow cost-effective batch production in the hospital pharmacy.

Influence of Experimental Cryptococcal Meningitis in Wistar Rats on Voriconazole Brain Penetration Assessed by Microdialysis

“…Despite its universally recognized toxicity, amphotericin B was considered to be the cornerstone for successful therapy in cryptococcal meningitis (1). The less toxic agent fluconazole (FCZ) offered an attractive alternative in the treatment of cryptococcosis and a variety of other invasive fungal infections in nonneutropenic patients (2,3); however, its use is limited due to resistance of Cryptococcus spp. (4).…”

Ultra-performance liquid chromatographic method for measurement of voriconazole in human plasma and oral fluid

“…In the 15 measured plasma concentrations, 3 were above the upper proposed threshold of 6 µg mL -1 and 2 were below the lower expected concentration of 1 µg mL -1 , with one third of all measurement outside the expected therapeutic range. The use of oral fluid for VRC TDM was previously described by Michael et al 9 and is supported by the physico-chemical characteristics of this drug, especially its pKa of 1.76 22 (with ionization being unaffected by usual mouth's pH) and its protein binding of 58%. 23 Interestingly, the percentage of oral fluid related to plasma concentration was relatively stable, ranging from 52.0-67.9%, with mean of 57.5%.…”

Implications of Storage Conditions on the Characteristics of Alginate Dialdehyde and Its Hydrogels

“…To use the stored solution for clinical applications, knowledge of storage stability and shelf life is important. [25] Literature documented stability studies of numerous compounds and drugs, including but not limited to human insulin, [26] Nacetylcysteine, [27,28] linezolid, [29] voriconazole, [30] dexmedetomidine, [31] and penicillin G. [32] To date, there are no reports investigating the storage stability of polysaccharide solutions designed for medical applications.…”