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Animals : an open access journal from MDPI2021; 11(7); 2047; doi: 10.3390/ani11072047

Nonlinear Mixed-Effect Pharmacokinetic Modeling and Distribution of Doxycycline in Healthy Female Donkeys after Multiple Intragastric Dosing-Preliminary Investigation.

Abstract: Doxycycline (DXC) is a broad-spectrum antibacterial antimicrobial administered to horses for the treatment of bacterial infections which may also affect donkeys. Donkeys have a different metabolism than horses, leading to differences in the pharmacokinetics of drugs compared to horses. This study aimed to describe the population pharmacokinetics of DXC in donkeys. Five doses of DXC hyclate (10 mg/kg) were administered via a nasogastric tube, q12 h, to eight non-fasted, healthy, adult jennies. Serum, urine, synovial fluid and endometrium were collected for 72 h following the first administration. Doxycycline concentration was measured by competitive enzyme immunoassay. Serum concentrations versus time data were fitted simultaneously using the stochastic approximation expectation-maximization algorithm for nonlinear mixed effects. A one-compartment model with linear elimination and first-order absorption after intragastric administration, best described the available pharmacokinetic data. Final parameter estimates indicate that DXC has a high volume of distribution (108 L/kg) as well as high absorption (10.3 h) in donkeys. However, results suggest that oral DXC at 10 mg/kg q12 h in donkeys would not result in a therapeutic concentration in serum, urine, synovial fluid or endometrium by comparison to the minimum inhibitory concentration of common equine pathogens. Further studies are recommended to identify appropriate dosage and dosing intervals of oral DXC in donkeys.
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Publication Date: 2021-07-09 PubMed ID: 34359175PubMed Central: PMC8300337DOI: 10.3390/ani11072047Google Scholar: Lookup
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  • 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 study investigates how the antibiotic doxycycline is processed by female donkeys, revealing that the standard dosage for this medicine may not be effective in donkeys despite its widespread use in horses.

Research context and objectives

  • The study sought to understand the pharmacokinetics—or how a drug moves through the body—of doxycycline (DXC) in female donkeys. DXC is an antimicrobial drug used to treat bacterial infections in horses, and it’s also used in donkeys, which have different metabolic systems.
  • The researchers’ objective was to determine if DXC’s current standard dosage is effective in treating bacterial infections within donkeys’ unique metabolic context.

Method

  • The team administered five doses of DXC via a nasogastric tube to eight healthy, adult female donkeys. The doses were provided every 12 hours.
  • Samples of the donkeys’ serum, urine, synovial fluid, and endometrium were collected by the researchers over 72 hours following the first dose of DXC. This allowed the team to track the medicine’s progress through the donkeys’ bodies.
  • DXC concentration was then measured within these collected samples using competitive enzyme immunoassay, a laboratory technique used to measure the concentration of substances in biological fluids.

Data Analysis

  • The outcome was analyzed using a complex statistical method called the stochastic approximation expectation-maximization algorithm, within the context of nonlinear mixed effects, to discern patterns in the pharmacokinetics data.
  • The researchers concluded that a one-compartment model with linear elimination and first-order absorption explained best how DXC spread through the donkeys’ bodies following intragastric administration.

Research Findings and Recommendations

  • The researchers found that DXC has a high volume of distribution (108 L/kg) and high absorption (10.3 h) in donkeys. Despite this, the research indicated that a dosage of 10 mg/kg administered every 12 hours wouldn’t result in a therapeutic concentration in serum, urine, synovial fluid, or endometrium when compared to the minimum inhibitory concentration of common equine pathogens.
  • The team recommended further studies to identify appropriate dosage and dosing intervals for DXC treatment in donkeys to ensure effective treatment of bacterial infections.

Cite This Article

APA
Chapuis RJJ, Smith JS, French HM, Toka FN, Peterson EW, Little EL. (2021). Nonlinear Mixed-Effect Pharmacokinetic Modeling and Distribution of Doxycycline in Healthy Female Donkeys after Multiple Intragastric Dosing-Preliminary Investigation. Animals (Basel), 11(7), 2047. https://doi.org/10.3390/ani11072047

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 11
Issue: 7
PII: 2047

Researcher Affiliations

Chapuis, Ronan J J
  • Department of Clinical Sciences, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.
Smith, Joe S
  • Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
French, Hilari M
  • Department of Clinical Sciences, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.
Toka, Felix Ngosa
  • Department of Biomedical Sciences, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.
Peterson, Erik W
  • Department of Clinical Sciences, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.
Little, Erika L
  • Department of Clinical Sciences, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.

Grant Funding

  • 42001-2016 / Ross University School of Veterinary Medicine

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

This article has been cited 2 times.
  1. Ebner L, O O, Simon B, Lizarraga I, Smith J, Cox S. Pharmacokinetics of butorphanol following intravenous and intramuscular administration in donkeys: A preliminary study.. Front Vet Sci 2022;9:979794.
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  2. Desanti-Consoli H, Bouillon J, Chapuis RJJ. Equids' Core Vaccines Guidelines in North America: Considerations and Prospective.. Vaccines (Basel) 2022 Mar 4;10(3).
    doi: 10.3390/vaccines10030398pubmed: 35335029google scholar: lookup
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