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Home / Equine Research Bank / Naunyn Schmiedebergs Arch Pharmacol / Concentration of the macrolide antibiotic tulathromycin in b...
Naunyn-Schmiedeberg\'s archives of pharmacology2009; 381(2); 161-169; doi: 10.1007/s00210-009-0481-1

Concentration of the macrolide antibiotic tulathromycin in broncho-alveolar cells is influenced by comedication of rifampicin in foals.

Abstract: Macrolide antibiotics penetrate in the lung against steep concentration gradients into the epithelial lining fluid (ELF) and broncho-alveolar cells (BAC). Since they interact with ABCB1, ABCC2, and organic anion transporting proteins (OATPs), which are localized to lung tissue, pulmonary concentration may be influenced by rifampicin (RIF), an inducer and modulator of efflux and uptake transporters. We measured concentrations of tulathromycin (TM) in plasma, ELF and BAC in 21 warm-blooded foals 24 and 192 h after first and last intramuscular injection of 2.5 mg/kg TM once weekly for 6 weeks. In 11 foals, TM was combined with RIF (10 mg/kg twice daily), and mRNA expression of ABCB1 and ABCC2 in BAC was assessed before and after RIF. Affinity of TM to ABCB1 and ABCC2 was measured by transport assays using cell monolayers and membrane vesicles of MDCKII and 2008 cells transfected with ABCB1 and ABCC2, respectively. At steady state, TM concentrated manifold in ELF and BAC. Comedication of RIF significantly decreased the AUC of TM (18.5 +/- 4.0 versus 24.4 +/- 3.7 microg x h/ml, p < 0.05) and lowered its concentrations in plasma (24 h, 0.17 +/- 0.05 versus 0.24 +/- 0.05 microg/ml; 192 h, 0.05 +/- 0.01 versus 0.06 +/- 0.01 microg/ml) and BAC (24 h, 0.84 +/- 0.36 versus 1.56 +/- 1.02 microg/ml; 192 h, 0.60 +/- 0.23 versus 1.23 +/- 0.90 microg/ml, all p < 0.05). Treatment with rifampicin did not markedly induce ABCB1 and ABCC2 expression. TM had no affinity to ABCB1 and ABCC2 in vitro. Concentration of TM in the lung of foals was significantly lowered by comedication of rifampicin most likely caused by extrapulmonary mechanisms leading to lower plasma concentrations.
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Publication Date: 2009-12-15 PubMed ID: 20012942DOI: 10.1007/s00210-009-0481-1Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

The research explores how the antibiotic Tulathromycin’s concentration within broncho-alveolar cells in foals can be affected by the co-administration of another medication, Rifampicin.

Research Context and Methodology

  • The main focus of this study is to investigate the impact of rifampicin (RIF), an inducer and modulator of efflux and uptake transporters, on the pulmonary concentration of Tulathromycin (TM), a macrolide antibiotic used in foals. This is due to the antibiotic’s known interaction with ABCB1, ABCC2, and organic anion transporting proteins (OATPs) localized to lung tissue.
  • The study was conducted on 21 warm-blooded foals and the concentrations of TM in plasma, epithelial lining fluid (ELF), and broncho-alveolar cells (BAC) were measured at 24 and 192 hours after the first and last intramuscular injection of 2.5 mg/kg TM once weekly for 6 weeks. In 11 of these foals, TM was also administered with RIF (10 mg/kg twice daily).
  • In addition to measuring TM concentrations, researchers assessed the mRNA expression of the ABCB1 and ABCC2 transporters in BAC before and after administration of RIF. The affinity of TM to ABCB1 and ABCC2 was also measured through transport assays using cell monolayers and membrane vesicles of MDCKII and 2008 cells transfected with ABCB1 and ABCC2, respectively.

Research Findings

  • The results of the study revealed that in a steady-state, TM concentrated significantly in ELF and BAC.
  • However, combining the administration of TM with RIF led to a significant decrease in TM’s area under concentration-time curve (AUC) and its concentrations in plasma and BAC. This suggests that RIF may impact the effectiveness of TM due to lower concentrations.
  • While there were changes in TM concentration, RIF did not prominently induce the expression of the ABCB1 and ABCC2 transporters. Also, TM did not have any apparent affinity to ABCB1 and ABCC2 according to in vitro tests.

Conclusion and Implications

  • The key finding of the research is that the concentration of TM within the lungs of foals was notably lowered by the co-administration of RIF. This suggests that extrapulmonary mechanisms may be at play, leading to lower plasma concentrations.
  • This study plays an important role in understanding how the efficacy of medication may be affected by the co-administration of other drugs, specifically the impact of Rifampicin on the equipment and uptake of Tulathromycin in foal lung cells. This information is vital for effectively treating diseases in foals using these drugs.

Cite This Article

APA
Venner M, Peters J, Höhensteiger N, Schock B, Bornhorst A, Grube M, Adam U, Scheuch E, Weitschies W, Rosskopf D, Kroemer HK, Siegmund W. (2009). Concentration of the macrolide antibiotic tulathromycin in broncho-alveolar cells is influenced by comedication of rifampicin in foals. Naunyn Schmiedebergs Arch Pharmacol, 381(2), 161-169. https://doi.org/10.1007/s00210-009-0481-1

Publication

Naunyn-Schmiedeberg\'s archives of pharmacology
ISSN: 1432-1912
NlmUniqueID: 0326264
Country: Germany
Language: English
Volume: 381
Issue: 2
Pages: 161-169

Researcher Affiliations

Venner, Monica
  • Clinic for Horses, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany.
Peters, Jette
    Höhensteiger, Nina
      Schock, Birthe
        Bornhorst, Alexa
          Grube, Markus
            Adam, Ulrike
              Scheuch, Eberhard
                Weitschies, Werner
                  Rosskopf, Dieter
                    Kroemer, Heyo K
                      Siegmund, Werner

                        MeSH Terms

                        • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
                        • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
                        • Animals
                        • Anti-Bacterial Agents / analysis
                        • Anti-Bacterial Agents / blood
                        • Anti-Bacterial Agents / pharmacokinetics
                        • Antibiotics, Antitubercular / administration & dosage
                        • Antibiotics, Antitubercular / metabolism
                        • Antibiotics, Antitubercular / pharmacology
                        • Area Under Curve
                        • Bronchi / cytology
                        • Bronchi / metabolism
                        • Bronchoalveolar Lavage Fluid / chemistry
                        • Cell Line
                        • Disaccharides / analysis
                        • Disaccharides / blood
                        • Disaccharides / pharmacokinetics
                        • Dogs
                        • Drug Interactions
                        • Female
                        • Heterocyclic Compounds / analysis
                        • Heterocyclic Compounds / blood
                        • Heterocyclic Compounds / pharmacokinetics
                        • Horses
                        • Male
                        • Multidrug Resistance-Associated Protein 2
                        • Multidrug Resistance-Associated Proteins / biosynthesis
                        • Multidrug Resistance-Associated Proteins / genetics
                        • Pulmonary Alveoli / cytology
                        • Pulmonary Alveoli / metabolism
                        • RNA, Messenger / biosynthesis
                        • Rifampin / administration & dosage
                        • Rifampin / metabolism
                        • Rifampin / pharmacology

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                        Citations

                        This article has been cited 6 times.
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                          doi: 10.1111/jvp.70007pubmed: 40552784google scholar: lookup
                        3. 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.
                          doi: 10.3389/fphar.2024.1458496pubmed: 39624843google scholar: lookup
                        4. Rampacci E, Marenzoni ML, Chiaradia E, Passamonti F, Ricci M, Pepe M, Coletti M, Giovagnoli S. In vitro performances of novel co-spray-dried azithromycin/rifampicin microparticles for Rhodococcus equi disease treatment. Sci Rep 2018 Aug 14;8(1):12149.
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                        5. Rutenberg D, Venner M, Giguère S. Efficacy of Tulathromycin for the Treatment of Foals with Mild to Moderate Bronchopneumonia. J Vet Intern Med 2017 May;31(3):901-906.
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