Single-dose pharmacokinetics of orally administered metronidazole and intravenously administered imipenem in healthy horses and computer-based simulation of pleural fluid concentrations with multiple dosing.
Abstract: 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. Methods: 4 healthy Thoroughbreds. Methods: 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: 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.
Publication Date: 2020-09-25 PubMed ID: 32969731DOI: 10.2460/ajvr.81.10.783Google Scholar: Lookup
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- Journal Article
Summary
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The research study investigates how the medications metronidazole and imipenem disperse throughout the bodies of healthy horses after being administered in a single dose. The study also uses computer simulations to predict how the levels of these drugs in pleural fluid (fluid around the lungs) change after several doses.
Objective and Methodology
- The aim of the study was to identify the plasma pharmacokinetics of the antibiotics metronidazole and imipenem. These were administered orally and intravenously in a single dose to healthy Thoroughbred horses.
- The study also simulated the concentration of these drugs in the horses’ pleural fluid after they were administered every 8 hours.
- Four healthy Thoroughbred horses were used in the study.
- Pleural fluid and plasma samples were collected at predetermined intervals after administering the drugs. The makers of the study were particularly interested in the lowest concentrations of metronidazole and imipenem that could inhibit the growth of 90% of bacterial isolates, including 22 clinical isolates from horses with pleuropneumonia (a horse lung disease).
Results & Conclusions
- The study found that both metronidazole and imipenem penetrated the pleural fluid well. Concentrations of the drugs in pleural fluid were similar to those in plasma.
- In the computer simulation, the concentration of metronidazole in the pleural fluid was sufficient during 24 hours (ratio greater than 70) to inhibit bacteria. For imipenem, the pleural fluid concentration exceeded the minimum concentration to inhibit bacterial growth for more than half of the day.
- The study concluded that giving healthy horses metronidazole orally every 8 hours or imipenem intravenously every 8 hours resulted in suitable concentrations of these drugs in the pleural fluid. This suggests these administration regimes may be effective for treating pneumonia and pleuropneumonia caused by certain bacteria in horses.
Cite This Article
APA
Kuroda T, Nagata SI, Tamura N, Kinoshita Y, Niwa H, Mita H, Minami T, Fukuda K, Hobo S, Kuwano A.
(2020).
Single-dose pharmacokinetics of orally administered metronidazole and intravenously administered imipenem in healthy horses and computer-based simulation of pleural fluid concentrations with multiple dosing.
Am J Vet Res, 81(10), 783-789.
https://doi.org/10.2460/ajvr.81.10.783 Publication
Researcher Affiliations
MeSH Terms
- Animals
- Anti-Infective Agents
- Area Under Curve
- Computer Simulation
- Horses
- Imipenem
- Metronidazole
Citations
This article has been cited 1 times.- Kir F, Jusko WJ. Metronidazole Pharmacokinetics Across Species: Meta-Analysis Integrating Allometric Scaling and Minimal Physiologically-Based Pharmacokinetic Modeling. AAPS J 2025 Dec 5;28(1):25.
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