Measuring Methisazone Serum-Levels

Gomez, Christopher; Sandeman, T. F.

doi:10.1016/s0140-6736(66)92529-3

Cited by 1 publication

(1 citation statement)

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“…In one study, the maximum oral dosage of MZ was 6 grams per day for 4 days (i.e., up to 24 grams, total) [37]. Later reports indicated that peak serum concentrations of MZ reached up to 0.7 μg/mL following an oral treatment course of 40 mg/kg [39], or approximately 8 grams per treatment assuming a 70 kg adult weight. Although MZ is removed from the HydroVax-II vaccine preparation by performing Cellufine sulfate chromatography, if MZ was not removed, then the hypothetical dose of MZ in a 0.5 mL vaccine dose would be approximately 0.0025 gram.…”

Section: Discussionmentioning

confidence: 99%

Advanced oxidation technology for the development of a next-generation inactivated West Nile virus vaccine

Quintel

Thomas

DeRaad

et al. 2019

Vaccine

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West Nile virus (WNV) is the most frequent mosquito-borne disease reported in the continental United States and although an effective veterinary vaccine exists for horses, there is still no commercial vaccine approved for human use. We have previously tested a 3% hydrogen peroxide (H 2 O 2 )-based WNV inactivation approach termed, HydroVax, in Phase I clinical trials and the vaccine was found to be safe and modestly immunogenic. Here, we describe an advanced, nextgeneration oxidation approach (HydroVax-II) for the development of inactivated vaccines that utilizes reduced concentrations of H 2 O 2 in combination with copper (cupric ions, Cu 2+ ) complexed with the antiviral compound, methisazone (MZ). Further enhancement of this oxidative approach included the addition of a low percentage of formaldehyde, a cross-linking reagent with a different mechanism of action that, together with H 2 O 2 /Cu/MZ, provides a robust two-pronged approach to virus inactivation. Together, this new approach results in rapid virus inactivation while greatly improving the maintenance of WNV-specific neutralizing epitopes mapped across the three structural domains of the WNV envelope protein. In combination with more refined manufacturing techniques, this inactivation technology resulted in vaccine-mediated WNV-specific neutralizing antibody responses that were 130-fold higher than that observed using the first generation, H 2 O 2only vaccine approach and provided 100% protection against lethal WNV infection. This new approach to vaccine development represents an important area for future investigation with the potential not only for improving vaccines against WNV, but other clinically relevant viruses as well.

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Section: Discussionmentioning

confidence: 99%