Identification of flunixin glucuronide and depletion of flunixin and its marker residue in bovine milk.

Residues of flunixin [and its marker residue 5-hydroxyflunixin (5OHFLU)] were determined in milk from cows that intravenously received therapeutic doses of the drug. The samples were collected during each milking (every 12 h) for six consecutive days, and concentrations of flunixin and its metabolites were determined by the method with and without enzymatic hydrolysis (beta-glucuronidase). The highest flunixin concentration in milk was observed 12 h after dosing (2.4 ± 1.42 µg/kg, mean ± SD). Flunixin concentrations in the samples determined with enzymatic hydrolysis were significantly higher (P < 0.05), which suggests the transfer of flunixin glucuronide to the milk. Additionally, unambiguous identification of flunixin glucuronide in the bovine milk was performed with linear ion-trap mass spectrometry. The 5OHFLU concentrations analyzed without enzymatic hydrolysis (22.3 ± 16.04 µg/kg) were similar to this obtained with enzymatic hydrolysis. Flunixin and 5OHFLU concentrations dropped below the limits of detection at 48 h after last dosing.

Pharmacokinetics of flunixin in mature heifers following multiple intravenous administration.

The pharmacokinetics of flunixin meglumine was determined after its multiple (altogether 4 doses at 24-hours intervals) intravenous administration at a dose of 2.2 mg/kg body weight in six mature clinically healthy heifers. Plasma flunixin and its metabolite 5-hydroxyflunixin concentrations were analyzed with high-pressure liquid chromatography using an assay with a lower limit detection of 0.03 microg/ml for both substances. Plasma concentrations versus time curves were described by a two compartment open model. Mean plasma flunixin concentrations were similar on day 1 and 4, and than rapidly decreased (within 2 hours) from initial concentrations higher than 10 microg/ml to the concentrations lower than 1 microg/ml. The distribution phase of flunixin was short (t0.5 alpha = 0.29 +/- 0.16 and 0.18 +/- 0.04 on day 1 and 4, respectively) and the elimination phase was more prolonged (t0.5 beta = 3.30 +/- 0.60 and 3.26 +/- 0.22 on day 1 and 4, respectively). The mean residence time of flunixin was similar on day 1 (1.83 +/- 0.83) and 4 (1.88 +/- 0.46), and for 5-hydroxyflunixin this parameter was insignificantly (P > 0.05) higher on day 1 (5.49 +/- 2.22) as compared to that found on day 4 (3.99 +/- 2.17). The clearance of flunixin was similar on both examined days (0.23 +/- 0.12 on day 1 and 0.31 +/- 0.15 on day 4), and for 5-hydroxyflunixin was insignificantly (P > 0.05) lower on day 1 (2.37 +/- 1.21) as compared to that determined on day 4 (3.23 +/- 1.06). Our data indicate that multiple administration of flunixin did not alter significantly the parent drug and its metabolite concentrations in plasma, however may cause some small changes in pharmacokinetic parameters.

Mercury in neonatal scalp hair.

Total mercury levels (TML) were determined in 141 samples of maternal head and pubic hair and neonatal scalp hair. The mean mercury contents of maternal head and pubic hair were 1.88 and 1.10 mg kg-1, respectively, while the mean TML of neonatal hair was 0.11 mg kg-1. A statistically significant correlation was found between TMLs in neonatal and maternal hair. Significant inverse correlation was observed between the mercury concentration in the hair of a newborn and its birth weight. Reported findings provide evidence that the neonatal scalp hair mercury level may be a useful indicator of intrauterine exposure to mercury.

Women in dental surgeries: reproductive hazards in occupational exposure to metallic mercury.

Eighty-one women (45 dentists and 36 dental assistants) occupationally exposed to metallic mercury underwent a toxicoclinical examination. Total mercury lebels (TMLs) were determined in scalp and pubic hair by cold vapour AAS. Furthermore a detailed questionnaire study was made concerning adverse reproductive events. TMLs in the hair of the exposed women examined exceeded significantly those determined in the hair of 34 controls not exposed to mercury. All exposed women had continued working during pregnancy. There was a significant, positive association between TMLs in the hair of exposed women and the occurrence of reproductive failures in their history. The relation between TMLs in the scalp hair and the prevalence of menstrual cycle disorders was statistically significant. These findings indicate that dental work could be another occupational hazard with respect to reproductive processes.