Objective—To determine the pharmacokinetics and tissue distribution of minocycline in horses.
Animals—5 healthy Thoroughbred mares for the pharmacokinetic experiment and 6 healthy Thoroughbred mares for the tissue distribution experiment.
Procedures—Each mare was given 2.2 mg of minocycline hydrochloride/kg, IV. Blood samples were collected once before minocycline administration (0 hours) and 10 times within 48 hours after administration in the pharmacokinetics study, and 24 tissue samples were obtained at 0.5 and 3 hours in the distribution study.
Results—No adverse effects were observed in any of the mares after minocycline administration. The mean ± SD elimination half-life was 7.70 ± 1.91 hours. The total body clearance was 0.16 ± 0.04 L/h/kg, and the volume of distribution at steady state was 1.53 ± 0.09 L/kg. The percentage of plasma protein binding was 68.1 ± 2.6%. Plasma concentration of free minocycline was 0.12 μg/mL at 12 hours. Minocycline was not detected in brain tissue, CSF or aqueous humor at 0.5 hours; however, it was found in all tissues, except in the aqueous humor, at 3 hours.
Conclusions and Clinical Relevance—Clearance of minocycline in healthy mares was greater than that reported for humans. For effective treatment of infections with common equine pathogens, it will be necessary to administer minocycline at a dosage of 2.2 mg/kg, IV, every 12 hours. This drug could be useful for infections in many tissues, including the CNS. The pharmacokinetic and tissue distribution data should aid in the appropriate use of minocycline in horses. (Am J Vet Res 2010;71:1062–1066)
To investigate the pharmacokinetics and antihistaminic effects (pharmacodynamics) of olopatadine in a small population of healthy horses after administration via nasogastric tube.
4 healthy adult Thoroughbreds.
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.
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.
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.
4 healthy Thoroughbreds.
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%.
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.