Single-dose pharmacokinetics of oral metronidazole and iv imipenem

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. 2020 Oct;81(10):783-789. doi: 10.2460/ajvr.81.10.783.

Authors
Taisuke Kuroda, Shun-Ichi Nagata, Norihisa Tamura, Yuta Kinoshita, Hidekazu Niwa, Hiroshi Mita, Takuto Minami, Kentaro Fukuda, Seiji Hobo, Atsutoshi Kuwano

PMID: 32969731
DOI: 10.2460/ajvr.81.10.783

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.