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American journal of veterinary research2006; 67(10); 1681-1686; doi: 10.2460/ajvr.67.10.1681

Pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar cells of foals.

Abstract: To determine pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar (BAL) cells of foals. Methods: 6 healthy 2-to 3-week-old foals. Methods: In a crossover design, clarithromycin (7.5 mg/kg) was administered to each foal via IV and intragastric (IG) routes. After the initial IG administration, 5 additional doses were administered IG at 12-hour intervals. Concentrations of clarithromycin and its 14-hydroxy metabolite were measured in serum by use of high-performance liquid chromatography. A microbiologic assay was used to measure clarithromycin activity in serum, urine, peritoneal fluid, synovial fluid, CSF, pulmonary epithelial lining fluid (PELF), and BAL cells. Results: After IV administration, elimination half-life (5.4 hours) and mean +/- SD body clearance (1.27 +/- 0.25 L/h/kg) and apparent volume of distribution at steady state (10.4 +/- 2.1 L/kg) were determined for clarithromycin. The metabolite was detected in all 6 foals by 1 hour after clarithromycin administration. Oral bioavailability of clarithromycin was 57.3 +/- 12.0%. Maximum serum concentration of clarithromycin after multiple IG administrations was 0.88 +/- 0.19 microg/mL. After IG administration of multiple doses, clarithromycin concentrations in peritoneal fluid, CSF, and synovial fluid were similar to or lower than concentrations in serum, whereas concentrations in urine, PELF, and BAL cells were significantly higher than concentrations in serum. Conclusions: Oral administration of clarithromycin at 7.5 mg/kg every 12 hours maintains concentrations in serum, PELF, and BAL cells that are higher than the minimum inhibitory concentration (0.12 microg/mL) for Rhodococcus equiisolates for the entire 12-hour dosing interval.
Publication Date: 2006-10-04 PubMed ID: 17014316DOI: 10.2460/ajvr.67.10.1681Google Scholar: Lookup
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  • Clinical Trial
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research paper describes a study on the pharmacokinetics of clarithromycin in foals and its concentration level in various body fluids and bronchoalveolar (BAL) cells. The study provides insights into how the drug is absorbed, distributed, and eliminated in the body.

Methodology

  • The study was conducted on six healthy foals aged between two to three weeks.
  • The experimental design was a crossover in which, clarithromycin was administered to each foal via two routes – intravenously (IV) and intragastric (IG). The dosage used was 7.5 mg/kg.
  • Following the first IG administration, additional doses were given IG at 12-hour intervals, five times.
  • The concentrations of clarithromycin and its 14-hydroxy metabolite, which is the substance formed when the body processes clarithromycin, were measured in the serum using high-performance liquid chromatography, a technique used to identify, quantify and purify components of mixtures.
  • A microbiological assay, or a test to measure the effects of a substance on a living organism, was used to measure the activity of clarithromycin in a variety of body fluids, including serum, urine, peritoneal fluid, synovial fluid, cerebrospinal fluid (CSF), pulmonary epithelial lining fluid (PELF) and BAL cells.

Results

  • After IV administration of clarithromycin, the study determined the elimination half-life (time it takes for the concentration or amount of drug in the body to be reduced by one-half), body clearance rate, and the apparent volume of distribution at steady state.
  • The metabolite of clarithromycin was detected in all foals within one hour of administering the drug, indicating that the substance was readily processed in the body.
  • Oral bioavailability of clarithromycin, which refers to the extent and rate at which the active drug ingredient is absorbed and becomes available in the bloodstream, was found to be slightly over 57%.
  • The maximum concentration of clarithromycin in the serum after multiple IG administrations was 0.88 +/- 0.19 micrograms/mL.
  • Interestingly, after IG administration of multiple doses, the concentration of clarithromycin in peritoneal fluid, CSF and synovial fluid were comparable to or lower than that in the serum. However, the concentration in urine, PELF, and BAL cells were significantly higher than that in the serum.

Conclusions

  • It was found that oral administration of clarithromycin at a dosage of 7.5 mg/kg every 12 hours maintained concentrations in serum, PELF, and BAL cells that are higher than the minimum inhibitory concentration for Rhodococcus equi isolates for the entire dosing interval. The minimum inhibitory concentration is the lowest concentration of a drug that prevents visible growth of a bacterium. This suggests that the dosage and administration method were effective in managing bacterial growth.

Cite This Article

APA
Womble AY, Giguère S, Lee EA, Vickroy TW. (2006). Pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar cells of foals. Am J Vet Res, 67(10), 1681-1686. https://doi.org/10.2460/ajvr.67.10.1681

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 67
Issue: 10
Pages: 1681-1686

Researcher Affiliations

Womble, Ariel Y
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136, USA.
Giguère, Steeve
    Lee, Elise A
      Vickroy, Thomas W

        MeSH Terms

        • Administration, Oral
        • Animals
        • Anti-Bacterial Agents / administration & dosage
        • Anti-Bacterial Agents / blood
        • Anti-Bacterial Agents / pharmacokinetics
        • Anti-Bacterial Agents / urine
        • Area Under Curve
        • Ascitic Fluid / metabolism
        • Bronchoalveolar Lavage Fluid / cytology
        • Clarithromycin / administration & dosage
        • Clarithromycin / blood
        • Clarithromycin / pharmacokinetics
        • Clarithromycin / urine
        • Cross-Over Studies
        • Female
        • Half-Life
        • Horses / metabolism
        • Injections, Intravenous / veterinary
        • Male
        • Synovial Fluid / metabolism
        • Tissue Distribution

        Citations

        This article has been cited 8 times.
        1. 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).
          doi: 10.3390/antibiotics12040700pubmed: 37107062google scholar: lookup
        2. Hetrick K, Harkin KR, Peddireddi L, Henningson J. Evaluation by polymerase chain reaction assay of persistent shedding of pathogenic leptospires in the urine of dogs with leptospirosis. J Vet Intern Med 2022 Jan;36(1):133-140.
          doi: 10.1111/jvim.16309pubmed: 34799884google scholar: lookup
        3. Krzych ŁJ, Czok M, Putowski Z. Is Antimicrobial Treatment Effective During Therapeutic Plasma Exchange? Investigating the Role of Possible Interactions. Pharmaceutics 2020 Apr 25;12(5).
          doi: 10.3390/pharmaceutics12050395pubmed: 32344863google scholar: lookup
        4. Rodvold KA, George JM, Yoo L. Penetration of anti-infective agents into pulmonary epithelial lining fluid: focus on antibacterial agents. Clin Pharmacokinet 2011 Oct;50(10):637-64.
        5. Wimsatt J, Tothill A, Offermann CF, Sheehy JG, Peloquin CA. Long-term and per rectum disposition of Clarithromycin in the desert tortoise (Gopherus agassizii). J Am Assoc Lab Anim Sci 2008 Jul;47(4):41-5.
          pubmed: 18702450
        6. Hardefeldt L, Thomas K, Page S, Norris J, Browning G, El Hage C, Stewart A, Gilkerson J, Muscatello G, Verwilghen D, van Galen G, Bauquier J, Cuming R, Reynolds B, Whittaker C, Wilkes E, Clulow J, Burden C, Begg L. Antimicrobial prescribing guidelines for horses in Australia. Aust Vet J 2025 Dec;103(12):781-889.
          doi: 10.1111/avj.70003pubmed: 40903020google scholar: lookup
        7. Shah RV, Kipper K, Baker EH, Barker CIS, Oldfield I, Davidson HC, Swire CC, Philips BJ, Johnston A, Rhodes A, Sharland M, Standing JF, Lonsdale DO. Intravenous Clarithromycin in Critically Ill Adults: A Population Pharmacokinetic Study. Antibiotics (Basel) 2025 May 30;14(6).
          doi: 10.3390/antibiotics14060559pubmed: 40558149google scholar: lookup
        8. Baptiste KE, Kyvsgaard NC, Ahmed MO, Damborg P, Dowling PM. Is Rifampin (Rifampicin) Essential for the Treatment of Rhodococcus equi Infections in Foals? A Critical Review of the Role of Rifampin. J Vet Pharmacol Ther 2025 Sep;48(5):345-358.
          doi: 10.1111/jvp.70007pubmed: 40552784google scholar: lookup