ABSTRACT
The purpose of this study was to assess safety and alterations in body fluid concentrations of voriconazole in normal horses on days 7 and 14 following once daily dose of 4 mg/kg of voriconazole orally for 14 days. Body fluid drug concentrations were determined by the use of high performance liquid chromatography (HPLC). On day 7, mean voriconazole concentrations of plasma, peritoneal, synovial and cerebrospinal fluids, aqueous humor, epithelial lining fluid (ELF), and urine were 1.47 +/- 0.63, 0.61 +/- 0.22, 0.70 +/- 0.20, 0.62 +/- 0.26, 0.55 +/- 0.32, 79.45 +/- 69.4, and 1.83 +/- 0.44 microg/mL respectively. Mean voriconazole concentrations in the plasma, peritoneal, synovial and cerebrospinal fluids, aqueous humor, ELF and urine on day 14 were 1.60 +/- 0.37, 1.02 +/- 0.27, 0.86 +/- 0.25, 0.64 +/- 0.21, 0.68 +/- 0.13, 47.76 +/- 45.4 and 3.34 +/- 2.17 respectively. Voriconazole concentrations in the bronchoalveolar cell pellet were below the limit of detection. There was no statistically significant difference between voriconazole concentrations of body fluids when comparing days 7 and 14. Results indicated that voriconazole distributes widely into body fluids.
Subject(s)
Antifungal Agents/pharmacokinetics , Body Fluids/chemistry , Horses/metabolism , Pyrimidines/pharmacokinetics , Triazoles/pharmacokinetics , Animals , Antifungal Agents/administration & dosage , Antifungal Agents/chemistry , Antifungal Agents/metabolism , Drug Administration Schedule , Female , Pyrimidines/administration & dosage , Pyrimidines/chemistry , Pyrimidines/metabolism , Triazoles/administration & dosage , Triazoles/chemistry , Triazoles/metabolism , VoriconazoleABSTRACT
Five biomarkers (MT: metallothionein-like proteins, EROD: ethoxyresorufin ortho-dééthylase, DNA strand breaks, LPO: peroxidation of lipids, VG: vitellogenin-like protiens) were measured in the soft tissues of zebra mussels (Dreissena polymorpha) in order to assess the spatial variation of exposure to contaminants along the St Lawrence River (Canada). Fifteen mussels >25 mm shell length were analyzed from each of the 13 sampling sites. Significant differences between sites were noted for all biomarkers, but the general level of variability was low. Three biomarkers (DNA, LPO and VG) exhibited a similar pattern of spatial variation while MT and EROD had distinct and specific patterns. MT had the strongest discriminating power and EROD showed the largest range of variation among sites. Highest biomarker responses were measured in specimens from local contaminated sites such as harbors and industrial sectors. A positive relationship was found between MT and copper (Cu), but no significant correlation was observed between other biomarker responses and the levels of ten trace metals bioaccumulating in the zebra mussels tissues. Results indicate that the measurement of biomarker responses is technically feasible. The performance of each biomarker is assessed in the context of the role and advantages of selecting a battery of biomarkers for detecting contamination problems. The use of zebra mussels as a sentinel species for biomonitoring potential toxic effects in situ is discussed.
