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Plasma pharmacokinetics, pulmonary distribution, and in vitro activity of gamithromycin in foals.
Abstract: The objectives of this study were to determine the plasma and pulmonary disposition of gamithromycin in foals and to investigate the in vitro activity of the drug against Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) and Rhodococcus equi. A single dose of gamithromycin (6 mg/kg of body weight) was administered intramuscularly. Concentrations of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and blood neutrophils were determined using HPLC with tandem mass spectrometry detection. The minimum inhibitory concentration of gamithromycin required for growth inhibition of 90% of R. equi and S. zooepidemicus isolates (MIC(90)) was determined. Additionally, the activity of gamithromycin against intracellular R. equi was measured. Mean peak gamithromycin concentrations were significantly higher in blood neutrophils (8.35±1.77 μg/mL) and BAL cells (8.91±1.65 μg/mL) compared with PELF (2.15±2.78 μg/mL) and plasma (0.33±0.12 μg/mL). Mean terminal half-lives in neutrophils (78.6 h), BAL cells (70.3 h), and PELF (63.6 h) were significantly longer than those in plasma (39.1 h). The MIC(90) for S. zooepidemicus isolates was 0.125 μg/mL. The MIC of gamithromycin for macrolide-resistant R. equi isolates (MIC(90)=128 μg/mL) was significantly higher than that for macrolide-susceptible isolates (1.0 μg/mL). The activity of gamithromycin against intracellular R. equi was similar to that of azithromycin and erythromycin. Intramuscular administration of gamithromycin at a dosage of 6 mg/kg would maintain PELF concentrations above the MIC(90) for S. zooepidemicus and phagocytic cell concentrations above the MIC(90) for R. equi for approximately 7 days.
© 2011 Blackwell Publishing Ltd.
Publication Date: 2011-03-28 PubMed ID: 21443748DOI: 10.1111/j.1365-2885.2011.01292.xGoogle Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research investigates the distribution of the drug gamithromycin in the blood and lungs of foals, and its effectiveness in inhibiting harmful bacteria. It suggests that administering gamithromycin at a specific dosage can keep drug concentrations effective against certain bacteria in the lungs and blood cells for about a week.
Research Methodology
- The researchers used foals for this study, to whom they administered a single dose of gamithromycin intramuscularly.
- They followed up by determining the concentrations of the drug in plasma, Pulmonary Epithelial Lining Fluid (PELF), cells in the bronchoalveolar lavage (BAL – a procedure for washing out the lungs), and blood neutrophils (a type of immune cell).
- The detection of gamithromycin concentration used High-Performance Liquid Chromatography (HPLC) with tandem mass spectrometry detection, a sensitive and accurate method.
Findings
- In terms of distribution, researchers found that the peak concentrations of gamithromycin were significantly higher in blood neutrophils and BAL cells compared to PELF and plasma.
- They also discovered that the drug remains in neutrophils, BAL cells, and PELF for longer periods than it does in plasma (i.e., it has longer terminal half-lives in those areas).
- The study examined the inhibiting potential or “Minimum Inhibitory Concentration” (MIC) of gamithromycin against two bacteria that can cause infections in horses: Streptococcus equi subsp. zooepidemicus and Rhodococcus equi.
- The researchers found that the necessary MIC to inhibit 90% of S. zooepidemicus was 0.125 μg/mL, and also noted that the drug’s activity against intracellular R. equi was similar to other common antibiotics, azithromycin and erythromycin.
- However, for R. equi isolates resistant to macrolides (a class of antibiotics), the necessary MIC of gamithromycin was significantly higher.
Conclusion
- From the findings, the researchers concluded that administering gamithromycin at a dose of 6 mg/kg could maintain effective drug concentrations in the lung’s PELF against S. zooepidemicus, and in phagocytic cells (cells which protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells) against R. equi for approximately seven days.
- This suggests that gamithromycin could be effectively used as a treatment against these bacteria in horses.
Cite This Article
APA
Berghaus LJ, Giguère S, Sturgill TL, Bade D, Malinski TJ, Huang R.
(2011).
Plasma pharmacokinetics, pulmonary distribution, and in vitro activity of gamithromycin in foals.
J Vet Pharmacol Ther, 35(1), 59-66.
https://doi.org/10.1111/j.1365-2885.2011.01292.x Publication
Researcher Affiliations
- Department of Large Animal Medicine, University of Georgia, Athens, GA 30602, USA.
MeSH Terms
- Animals
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / metabolism
- Anti-Bacterial Agents / pharmacokinetics
- Female
- Horses / blood
- Horses / metabolism
- Lung / metabolism
- Macrolides / blood
- Macrolides / metabolism
- Macrolides / pharmacokinetics
- Male
- Microbial Sensitivity Tests
- Rhodococcus equi / drug effects
- Streptococcus equi / drug effects
- Tissue Distribution
Citations
This article has been cited 11 times.- Zúñiga MP, Badillo E, Abalos P, Valencia ED, Marín P, Escudero E, Galecio JS. Antimicrobial susceptibility of Rhodococcus equi strains isolated from foals in Chile. World J Microbiol Biotechnol 2023 Jun 22;39(9):231.
- Wang J, Zhou X, Elazab ST, Park SC, Hsu WH. Should Airway Interstitial Fluid Be Used to Evaluate the Pharmacokinetics of Macrolide Antibiotics for Dose Regimen Determination in Respiratory Infection?. Antibiotics (Basel) 2023 Apr 3;12(4).
- Blondeau JM. Immunomodulatory Effects of Macrolides Considering Evidence from Human and Veterinary Medicine. Microorganisms 2022 Dec 9;10(12).
- Hamel D, Richard-Mazet A, Voisin F, Böhne I, Fraisse F, Rauh R, Huang R, Kellermann M, Letendre L, Dumont P, Rehbein S. Gamithromycin in swine: Pharmacokinetics and clinical evaluation against swine respiratory disease. Vet Med Sci 2021 Mar;7(2):455-464.
- Mzyk DA, Bublitz CM, Martinez MN, Davis JL, Baynes RE, Smith GW. Impact of bovine respiratory disease on the pharmacokinetics of danofloxacin and tulathromycin in different ages of calves. PLoS One 2019;14(6):e0218864.
- Hildebrand F, Venner M, Giguère S. Efficacy of gamithromycin for the treatment of foals with mild to moderate bronchopneumonia. J Vet Intern Med 2015 Jan;29(1):333-8.
- Huguet A-S, Gourbeyre O, Bousquet-Mélou A, Ferran AA, Lallemand EA. Reassessment of extracellular and intracellular activity of macrolides, rifampicin, and doxycycline against Rhodococcus equi based on bacterial counts and microscopy. Microbiol Spectr 2025 Sep 2;13(9):e0120525.
- Boneva-Marutsova B, Marutsov P, Kerner K, Zhelev G. First Detection of Rhodococcus equi in a Foal in Bulgaria-A Case Report. Animals (Basel) 2025 Jul 12;15(14).
- Huguet AS, Gourbeyre O, Bernand A, Philibert C, Bousquet-Melou A, Lallemand EA, Ferran AA. Comparative bactericidal activity of four macrolides alone and combined with rifampicin or doxycycline against Rhodococcus equi at concentrations achievable in foals. Front Pharmacol 2024;15:1458496.
- Wei XY, Zhang J, Zhang Y, Fu WZ, Zhong LG, Pan YD, Sun J, Liao XP, Liu YH, Zhou YF. Pharmacokinetic/pharmacodynamic evaluation of gamithromycin against rabbit pasteurellosis. BMC Vet Res 2024 Apr 20;20(1):147.
- Giguère S, Berghaus LJ, Willingham-Lane JM. Antimicrobial Resistance in Rhodococcus equi. Microbiol Spectr 2017 Oct;5(5).
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