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Home / Equine Research Bank / Acta Vet Scand / Pharmacokinetics of a peroral single dose of two long-acting...
Acta veterinaria Scandinavica2013; 55(1); 21; doi: 10.1186/1751-0147-55-21

Pharmacokinetics of a peroral single dose of two long-acting formulations and an aqueous formulation of doxycycline hyclate in horses.

Abstract: Doxycyline (Dox) is a semisynthetic antibacterial drug with pharmacological advantages over its parent drug (tetracycline) in the treatment of various bacterial diseases in horses. Yet, at present a horse-customized pharmaceutical formulation is not available. Based on its pharmacokinetic/pharmacodynamic (PK/PD) ratio, Dox is considered a time-dependent antibacterial drug and ideally expected to achieve sustained plasma drug concentrations both at or slightly above the minimal inhibitory concentration (MIC) level for as long as possible between dosing intervals. Hence, the objective of this study was to formulate two long-acting (LA) doxycyline hyclate (Dox-h) formulations for oral administration and define their pharmacokinetics in non-fasted adult horses to obtain better bioavailability and longer mean residence time, features needed to comply better with its pharmacokinetic/pharmacodynamic (PK/PD) ratios. Results: Pharmacokinetic parameters were determined after the oral administration of a single 10 mg/kg bolus dose of two 20% Dox-h formulations: one based on a β cyclodextrin (Dox-β) matrix and a second one on a poloxamer (Dox-pol) matrix. The results were compared with the pharmacokinetics of a single 10 mg/kg bolus oral dose of a freshly made aqueous Dox-h solution (Dox-a). Dox-pol showed the greatest values for relative bioavailability (548%); maximum serum concentration (Cmax) value was 1.3 ± 0.7 μg/mL with time to reach the Cmax (Tmax) of 5.9 ± 1.7 h, area under the curve (AUC) of 17.0 ± 2.2 μg h/ml and elimination half-life (T½ β) of 4.9 ± 1.0 h. Conclusions: Considering a minimal inhibitory concentration MIC of 0.25 μg/mL, clinically effective plasma concentrations might be obtained for up to 24 h administering Dox-pol. This is an oral paste formulation that might optimize the use of Dox-h in horses in terms of PK/PD ratio congruency, and it is likely that it may also improve prescription compliance due to its ease of administration.
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Publication Date: 2013-03-08 PubMed ID: 23497696PubMed Central: PMC3608154DOI: 10.1186/1751-0147-55-21Google Scholar: Lookup
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  • Clinical Trial
  • 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.

The research article focuses on developing two long-acting oral formulations of the antibacterial drug Doxycycline Hyclate (Dox-h) for effective treatment of bacterial diseases in horses. The study evaluates the pharmacokinetics of these formulations with the aim of achieving sustained and effective plasma drug levels in the horse’s system.

Objective of the Study

  • The main aim was to establish two long-acting oral formulations of Doxycycline Hyclate for horses. The drug is deemed a time-dependent antibacterial agent and needs to consistently maintain a specific plasma concentration to yield maximum therapeutic benefit.
  • The creation of such formulations would allow patients to maintain treatment effectiveness while reducing dosage frequency, eventually leading to improved treatment compliance.

Methodology and Results

  • The research team explored the pharmacokinetics of two formulated versions of the antibacterial drug: one based on a β cyclodextrin matrix (Dox-β) and a second based on a poloxamer matrix (Dox-pol).
  • The team used a single 10 mg/kg dose of each formulation and compared the results with the pharmacokinetics of a freshly made aqueous solution of Dox-h (Dox-a).
  • The study discovered that Dox-pol had the highest relative bioavailability (548%), with the highest potential for sustained therapeutic plasma concentration.

Conclusions and Implications

  • Given the minimum inhibitory concentration (MIC) of the drug, which is 0.25 μg/mL, the Dox-pol formulation could maintain effective plasma concentrations for up to 24 hours. This result has significant implications for improving treatment effectiveness and compliance in horses.
  • Essentially, this research paves the way for enhancing the use of Dox-h in horse health care, potentially leading to better treatment outcomes for bacterial diseases and enhancing the quality of equine healthcare.

Cite This Article

APA
Zozaya H, Gutierrez L, Bernad MJ, Sumano H. (2013). Pharmacokinetics of a peroral single dose of two long-acting formulations and an aqueous formulation of doxycycline hyclate in horses. Acta Vet Scand, 55(1), 21. https://doi.org/10.1186/1751-0147-55-21

Publication

Acta veterinaria Scandinavica
ISSN: 1751-0147
NlmUniqueID: 0370400
Country: England
Language: English
Volume: 55
Issue: 1
Pages: 21

Researcher Affiliations

Zozaya, Heidi
  • Department of Physiology and Pharmacology, School of Veterinary Medicine, National Autonomous University of Mexico (UNAM), Av, Universidad 3000, Coyoacan Mexico City 04360, Mexico.
Gutierrez, Lilia
    Bernad, Maria Josefa
      Sumano, Hector

        MeSH Terms

        • Absorption
        • Administration, Oral
        • Animals
        • Anti-Bacterial Agents / administration & dosage
        • Anti-Bacterial Agents / pharmacokinetics
        • Area Under Curve
        • Doxycycline / administration & dosage
        • Doxycycline / pharmacokinetics
        • Female
        • Half-Life
        • Horses / blood
        • Horses / metabolism
        • Male

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        Citations

        This article has been cited 5 times.
        1. Song Y, Day CM, Afinjuomo F, Tan JE, Page SW, Garg S. Advanced Strategies of Drug Delivery via Oral, Topical, and Parenteral Administration Routes: Where Do Equine Medications Stand?. Pharmaceutics 2023 Jan 4;15(1).
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        2. Larsen EA, Lack AC, Wassack E. Case report: Use of penicillin G potassium in poloxamer 407 gel to aid in healing of an equine sublingual abscess. Front Vet Sci 2022;9:783753.
          doi: 10.3389/fvets.2022.783753pubmed: 35968007google scholar: lookup
        3. Chapuis RJJ, Smith JS, French HM, Toka FN, Peterson EW, Little EL. Nonlinear Mixed-Effect Pharmacokinetic Modeling and Distribution of Doxycycline in Healthy Female Donkeys after Multiple Intragastric Dosing-Preliminary Investigation. Animals (Basel) 2021 Jul 9;11(7).
          doi: 10.3390/ani11072047pubmed: 34359175google scholar: lookup
        4. Franklin RK, Marcus SA, Talaat AM, KuKanich BK, Sullivan R, Krugner-Higby LA, Heath TD. A Novel Loading Method for Doxycycline Liposomes for Intracellular Drug Delivery: Characterization of In Vitro and In Vivo Release Kinetics and Efficacy in a J774A.1 Cell Line Model of Mycobacterium smegmatis Infection. Drug Metab Dispos 2015 Aug;43(8):1236-45.
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        5. Martínez J, Escudero E, Badillo E, Yuste MT, Galecio JS, Marin P. Pharmacokinetics of Doxycycline in Plasma and Milk after Intravenous and Intramuscular Administration in Dairy Goats. Animals (Basel) 2024 Aug 20;14(16).
          doi: 10.3390/ani14162416pubmed: 39199950google scholar: lookup
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