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- Author or Editor: Taisuke Kuroda x
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Abstract
OBJECTIVE
To investigate the pharmacokinetics and antihistaminic effects (pharmacodynamics) of olopatadine in a small population of healthy horses after administration via nasogastric tube.
ANIMALS
4 healthy adult Thoroughbreds.
PROCEDURES
Olopatadine (0.1 mg/kg, once) was administered via nasogastric tube. Blood samples were collected at predetermined time points for pharmacokinetic analyses of the drug in plasma. Olopatadine effects were investigated by measurement of cutaneous wheals induced by ID histamine injection (0.1 mL [10 μg]/injection) at predetermined time points. Inhibition effect ratios were calculated on the basis of measured wheal size (area) after versus before olopatadine administration.
RESULTS
Mean ± SD maximum plasma olopatadine concentration was 48.8 ± 11.0 ng/mL approximately 1.5 hours after administration. Median terminal half-life was 6.11 hours. Mean ± SD maximal effect was 88.2 ± 4.9% inhibition approximately 3.5 hours after drug delivery, and the inhibition effect remained > 80% for 12.5 hours after treatment. No signs of adverse clinical effects were observed.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested olopatadine may have a strong, long-term inhibitory effect against histamine-induced wheals in the skin of horses. Clinical research with a larger number of horses is warranted.
Abstract
OBJECTIVE
To determine plasma pharmacokinetics of metronidazole and imipenem following administration of a single dose PO (metronidazole, 15 mg/kg) or IV (imipenem, 10 mg/kg) in healthy Thoroughbreds and simulate pleural fluid concentrations following multiple dose administration every 8 hours.
ANIMALS
4 healthy Thoroughbreds.
PROCEDURES
Metronidazole and imipenem were administered, and samples of plasma and pleural fluid were collected at predetermined time points. Minimum concentrations of metronidazole and imipenem that inhibited growth of 90% of isolates (MIC90), including 22 clinical Bacteroides isolates from horses with pleuropneumonia, were calculated. For the computer simulation, the target ratio for area under the pleural fluid concentration-versus-time curve during 24 hours to the MIC90 for metronidazole was > 70, and the target percentage of time per day that the pleural fluid concentration of imipenem exceeded the MIC90 was > 50%.
RESULTS
Mean ± SD pleural fluid concentrations of metronidazole and imipenem were 12.7 ± 3.3 μg/mL and 12.1 ± 0.9 μg/mL, respectively, 1 hour after administration and 4.9 ± 0.85 μg/mL and 0.3 ± 0.08 μg/mL, respectively, 8 hours after administration. For both antimicrobials, concentrations in the pleural fluid and plasma were similar. The ratio for area under the pleural fluid concentration-versus-time curve during 24 hours to the MIC90 for metronidazole was 84.9, and the percentage of time per day the pleural fluid concentration of imipenem exceeded the MIC90 was 70.9%.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested that administration of metronidazole (15 mg/kg, PO, q 8 h) or imipenem (10 mg/kg, IV, q 8 h) resulted in their accumulation in the pleural fluid in healthy horses and concentrations were likely to be effective for the treatment of pneumonia and pleuropneumonia caused by Bacteroides spp.
