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- Author or Editor: Dawn M. Boothe x
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Abstract
OBJECTIVE
To determine antibiotic levels in plasma and interstitial fluid (ISF) after SC placement of compounded florfenicol (FF) calcium sulfate beads (CSBs) in New Zealand White rabbits (Oryctolagus cuniculus).
ANIMALS
6 juvenile female rabbits (n = 5 treatment and 1 control).
METHODS
An ultrafiltration probe and CSBs were placed SC in 6 rabbits (n = 5 for FF CSBs and 1 for control CSBs). Plasma (3, 6, 12, 24, and 48 hours and 7, 14, and 21 days) and ISF (daily for 21 days) samples were collected, and FF was measured by HPLC for pharmacokinetic analysis. Hematology, biochemistry, and histopathology were assessed.
RESULTS
Means ± SD for the area under the curve, maximum concentration, time of maximum concentration, terminal half-life, and mean residence time to the last data point for plasma and ISF were 16.63 ± 8.16 and 17,902 ± 7,564 h·µg/mL, 0.79 ± 0.38 and 245 ± 223 µg/mL, 2.90 ± 0.3 and 59 ± 40 hours, 30.81 ± 16.9 and 27.3 ± 9.39 hours, 23.4 ± 10 and 73.7 ± 13 hours, respectively. Plasma FF was < 2 µg/mL at all time points. The ISF FF remained > 8 μg/mL for 109.98 to 231.58 hours. One rabbit death occurred during treatment, but the cause of death was undetermined. Local tissue inflammation was present, but no clinically significant systemic adverse effects were found on hematology, biochemistry, or histopathology in the remaining rabbits.
CLINICAL RELEVANCE
Florfenicol CSBs maintained antibiotic concentrations in ISF at levels likely to be effective against bacteria sensitive to > 8 µg/mL for 5 to 10 days while maintaining low (< 2 µg/mL) plasma levels. Florfenicol CSBs may be effective for local antibiotic treatment in rabbit abscesses.
Abstract
OBJECTIVE
To describe misoprostol pharmacokinetics and anti-inflammatory efficacy when administered orally or per rectum in endotoxin-challenged horses.
ANIMALS
6 healthy geldings.
PROCEDURES
A randomized 3-treatment crossover design was performed with a minimum washout period of 28 days between treatment arms. Prior to endotoxin challenge (lipopolysaccharide, 30 ng/kg IV over 30 minutes), horses received misoprostol (5 µg/kg once) per os (M-PO) or per rectum (M-PR) or water as control (CON). Clinical parameters were evaluated and blood samples obtained to measure plasma misoprostol free acid concentration, leukocyte counts, and tumor necrosis factor-α (TNFα) and interleukin 6 (IL-6) leukocyte gene expression and serum concentrations.
RESULTS
In the M-PO treatment arm, maximum plasma concentration and area under the concentration-versus-time curve (mean ± SD) were higher (5,209 ± 3,487 pg/mL and 17,998,254 ± 13,194,420 h·pg/mL, respectively) and median (interquartile range) time to maximum concentration (25 min [18 to 34 min]) was longer than in the M-PR treatment arm (854 ± 855 pg/mL; 644,960 ± 558,866 h·pg/mL; 3 min [3 to 3.5 min]). Significant differences in clinical parameters, leukocyte counts, and TNFα or IL-6 gene expression or serum protein concentration were not detected. Downregulation of relative gene expression was appreciated for individual horses in the M-PO and M-PR treatment arms at select time points.
CLINICAL RELEVANCE
Considerable variability in measured parameters was detected among horses within and between treatment arms. Misoprostol absorption and systemic exposure after PO administration differed from previous reports in horses not administered LPS. Investigation of multidose administration of misoprostol is warranted to better evaluate efficacy as an anti-inflammatory therapeutic.
Abstract
OBJECTIVE
To compare the pharmacokinetics between repeated doses and to characterize changes in the fecal microbiome after oral and rectal multidose misoprostol administration.
ANIMALS
6 healthy university-owned geldings.
PROCEDURES
In a randomized, crossover study, misoprostol (5 μg/kg) was administered orally or rectally every 8 hours for 10 doses, or not administered (control), with a 21-day washout between treatments. Concentration-versus-time data for dose 1 and dose 10 were subject to noncompartmental analysis. For microbiota analysis using 16S rRNA amplicon sequencing, manure was collected 7 days before study onset, immediately before dose 1, and 6 hours, 7 days, and 14 days after dose 10, with time-matched points in controls.
RESULTS
Repeated dosing-related differences in pharmacokinetic parameters were not detected for either administration route. The area under the concentration-versus-time curve was greater (P < .04) after oral versus rectal administration. The relative bioavailability of rectal administration was 4 to 86% of that of oral administration. Microbial composition, richness, and β-diversity differed among subjects (P < .001 all) while only composition differed between treatments (P ≤ .01). Richness was decreased 6 hours after dose 10 and at the control-matched time point (P = .0109) in all subjects. No other differences for time points, treatments, or their interactions were observed.
CLINICAL RELEVANCE
Differences in systemic exposure were associated with the route of administration but were not detected after repeated administration of misoprostol. Differences in microbiota parameters were primarily associated with interindividual variation and management rather than misoprostol administration.
