• 1.

    Huang RA, Letendre LT, Banav N, et al. Pharmacokinetics of gamithromycin in cattle with comparison of plasma and lung tissue concentrations and plasma antibacterial activity. J Vet Pharmacol Ther 2010; 33:227237.

    • Search Google Scholar
    • Export Citation
  • 2.

    Drusano GL. Infection site concentrations: their therapeutic importance and the macrolide and macrolide-like class of antibiotics. Pharmacotherapy 2005; 25:150S158S.

    • Search Google Scholar
    • Export Citation
  • 3.

    Godinho KS. Susceptibility testing of tulathromycin: interpretative breakpoints and susceptibility of field isolates. Vet Microbiol 2008; 129:426432.

    • Search Google Scholar
    • Export Citation
  • 4.

    Modric S, Webb AI, Derendorf H. Pharmacokinetics and pharmacodynamics of tilmicosin in sheep and cattle. J Vet Pharmacol Ther 1998; 21:444452.

    • Search Google Scholar
    • Export Citation
  • 5.

    Shryock TR, White DW, Staples JM, et al. Minimum inhibitory concentration breakpoints and disk diffusion inhibitory zone interpretive criteria for tilmicosin susceptibility testing against Pasteurella spp. associated with bovine respiratory disease. J Vet Diagn Invest 1996; 8:337344.

    • Search Google Scholar
    • Export Citation
  • 6.

    Nowakowski MA, Inskeep PB, Risk JE, et al. Pharmacokinetics and lung tissue concentrations of tulathromycin, a new triamilide antibiotic, in cattle. Vet Ther 2004; 5:6074.

    • Search Google Scholar
    • Export Citation
  • 7.

    Schunicht OC, Booker CW, Guichon PT, et al. An evaluation of the relative efficacy of tulathromycin for the treatment of undifferentiated fever in feedlot calves in Nebraska. Can Vet J 2007; 48:600606.

    • Search Google Scholar
    • Export Citation
  • 8.

    Kempf I, Reeve-Johnson L, Gesbert F, et al. Efficacy of tilmicosin in the control of experimental Mycoplasma gallisepticum infection in chickens. Avian Dis 1997; 41:802807.

    • Search Google Scholar
    • Export Citation
  • 9.

    Baldwin DR, Honeybourne D, Wise R. Pulmonary disposition of antimicrobial agents: methodological considerations. Antimicrob Agents Chemother 1992; 36:11711175.

    • Search Google Scholar
    • Export Citation
  • 10.

    Conte JE, Golden J, Duncan S, et al. Single-dose intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime in volunteer subjects. Antimicrob Agents Chemother 1996; 40:16171622.

    • Search Google Scholar
    • Export Citation
  • 11.

    Rennard SI, Basset G, Lecossier D, et al. Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Appl Physiol 1986; 60:532538.

    • Search Google Scholar
    • Export Citation
  • 12.

    Scorneaux B, Shryock TR. The determination of the cellular volume of avian, porcine and bovine phagocytes and bovine mammary epithelial cells and its relationship to uptake of tilmicosin. J Vet Pharmacol Ther 1999; 22:612.

    • Search Google Scholar
    • Export Citation
  • 13.

    Nix DE, Goodwin SD, Peloquin CA, et al. Antibiotic tissue penetration and its relevance: impact of tissue penetration on infection response. Antimicrob Agents Chemother 1991; 35:19531959.

    • Search Google Scholar
    • Export Citation
  • 14.

    Baldwin DR, Honeybourne D, Wise R. Pulmonary disposition of antimicrobial agents: in vivo observations and clinical relevance. Antimicrob Agents Chemother 1992; 36:11761180.

    • Search Google Scholar
    • Export Citation
  • 15.

    Nix DE, Goodwin SD, Peloquin CA, et al. Antibiotic tissue penetration and its relevance: models of tissue penetration and their meaning. Antimicrob Agents Chemother 1991; 35:19471952.

    • Search Google Scholar
    • Export Citation
  • 16.

    Kiem S, Schentag JJ. Interpretation of antibiotic concentration ratios measured in epithelial lining fluid. Antimicrob Agents Chemother 2008; 52:2436.

    • Search Google Scholar
    • Export Citation
  • 17.

    Fietta A, Merlini C, Gialdroni GG. Inhibition of intracellular growth of Staphylococcus aureus by exposure of infected human monocytes to clarithromycin and azithromycin. J Chemother 1997; 9:1722.

    • Search Google Scholar
    • Export Citation
  • 18.

    Labro MT. Intracellular bioactivity of macrolides. Clin Microbiol Infect 1996; 1 (suppl 1):S24S30.

  • 19.

    Mandell GL, Coleman E. Uptake, transport, and delivery of antimicrobial agents by human polymorphonuclear neutrophils. Antimicrob Agents Chemother 2001; 45:17941798.

    • Search Google Scholar
    • Export Citation
  • 20.

    Retsema JA, Bergeron JM, Girard D, et al. Preferential concentration of azithromycin in an infected mouse thigh model. J Antimicrob Chemother 1993; 31(suppl E):516.

    • Search Google Scholar
    • Export Citation
  • 21.

    Maglio D, Capitano B, Banevicius MA, et al. Differential efficacy of clarithromycin in lung versus thigh infection models. Chemotherapy 2004; 50:6366.

    • Search Google Scholar
    • Export Citation

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Disposition of gamithromycin in plasma, pulmonary epithelial lining fluid, bronchoalveolar cells, and lung tissue in cattle

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  • 1 Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
  • | 2 Pharmacokinetics and Drug Metabolism, Merial Limited, 631 US Hwy 1, North Brunswick, NJ 08902.
  • | 3 Pharmaceutical Research and Development, Merial Limited, 3239 Satellite Blvd, 500, Duluth, GA 30096.
  • | 4 Pharmaceutical Research and Development, Merial Limited, 3239 Satellite Blvd, 500, Duluth, GA 30096.
  • | 5 Pharmaceutical Research and Development, Merial Limited, 3239 Satellite Blvd, 500, Duluth, GA 30096.
  • | 6 Pharmaceutical Research and Development, Merial Limited, 3239 Satellite Blvd, 500, Duluth, GA 30096.

Abstract

Objective—To determine the disposition of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and lung tissue homogenate in cattle.

Animals—33 healthy Angus calves approximately 7 to 8 months of age.

Procedures—Calves were randomly assigned to 1 of 11 groups consisting of 3 calves each, which differed with respect to sample collection times. In 10 groups, 1 dose of gamithromycin (6 mg/kg) was administered SC in the neck of each calf (0 hours). The remaining 3 calves were not treated. Gamithromycin concentrations in plasma, PELF, lung tissue homogenate, and BAL cells (matrix) were measured at various points by means of high-performance liquid chromatography with tandem mass spectrometry.

Results—Time to maximum gamithromycin concentration was achieved at 1 hour for plasma, 12 hours for lung tissue, and 24 hours for PELF and BAL cells. Maximum gamithromycin concentration was 27.8 μg/g, 17.8 μg/mL, 4.61 μg/mL, and 0.433 μg/mL in lung tissue, BAL cells, PELF, and plasma, respectively. Terminal half-life was longer in BAL cells (125.0 hours) than in lung tissue (93.0 hours), plasma (62.0 hours), and PELF (50.6 hours). The ratio of matrix to plasma concentrations ranged between 4.7 and 127 for PELF, 16 and 650 for lung tissue, and 3.2 and 2,135 for BAL cells.

Conclusions and Clinical Relevance—Gamithromycin was rapidly absorbed after SC administration. Potentially therapeutic concentrations were achieved in PELF, BAL cells, and lung tissue within 30 minutes after administration and persisted for 7 (PELF) to > 15 (BAL cells and lung tissue) days after administration of a single dose.

Abstract

Objective—To determine the disposition of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and lung tissue homogenate in cattle.

Animals—33 healthy Angus calves approximately 7 to 8 months of age.

Procedures—Calves were randomly assigned to 1 of 11 groups consisting of 3 calves each, which differed with respect to sample collection times. In 10 groups, 1 dose of gamithromycin (6 mg/kg) was administered SC in the neck of each calf (0 hours). The remaining 3 calves were not treated. Gamithromycin concentrations in plasma, PELF, lung tissue homogenate, and BAL cells (matrix) were measured at various points by means of high-performance liquid chromatography with tandem mass spectrometry.

Results—Time to maximum gamithromycin concentration was achieved at 1 hour for plasma, 12 hours for lung tissue, and 24 hours for PELF and BAL cells. Maximum gamithromycin concentration was 27.8 μg/g, 17.8 μg/mL, 4.61 μg/mL, and 0.433 μg/mL in lung tissue, BAL cells, PELF, and plasma, respectively. Terminal half-life was longer in BAL cells (125.0 hours) than in lung tissue (93.0 hours), plasma (62.0 hours), and PELF (50.6 hours). The ratio of matrix to plasma concentrations ranged between 4.7 and 127 for PELF, 16 and 650 for lung tissue, and 3.2 and 2,135 for BAL cells.

Conclusions and Clinical Relevance—Gamithromycin was rapidly absorbed after SC administration. Potentially therapeutic concentrations were achieved in PELF, BAL cells, and lung tissue within 30 minutes after administration and persisted for 7 (PELF) to > 15 (BAL cells and lung tissue) days after administration of a single dose.

Contributor Notes

Supported by Merial Limited.

The authors thank Amanda J. Mullins and Jonathan F. Bader for analytic and technical assistance.

Address correspondence to Dr. Giguère (gigueres@uga.edu).