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Veterinary surgery : VS2024; doi: 10.1111/vsu.14128

Evaluation of pharmacokinetics of metoclopramide administered via subcutaneous bolus and intravenous constant rate infusion to adult horses.

Abstract: To determine the pharmacokinetics (PK) of metoclopramide administered via intravenous continuous rate infusion (IV CRI) and subcutaneous (SC) bolus and evaluate for gastrointestinal motility and adverse side effects. Methods: Experimental study; randomized, crossover design. Methods: Six healthy adult horses. Methods: Each horse received metoclopramide via IV CRI (0.04 mg/kg/h for 24 h) and SC bolus (0.08 mg/kg once), with ≥1 week washout period between. Plasma was analyzed by UPLC-MS/MS. Compartmental modeling was used to determine PK parameters for each treatment; nonparametric superposition was used to simulate multiple SC bolus regimens. Gastrointestinal motility and evidence of adverse effects were monitored. Results: T (h) for SC bolus was 0.583 ± 0.204 versus 17.3 ± 6.41 for IV CRI, while C (ng/mL) was 27.7 ± 6.38 versus 43.6 ± 9.97, respectively. AUC (h × ng/mL) was calculated as 902 ± 189 for 24 h IV CRI versus 244 ± 37.4 simulated for 0.08 mg/kg SC bolus every 8 h. Simulations revealed similar exposure between groups with administration of 0.96 mg/kg/day SC bolus, divided into three, four, or six doses. SC bolus bioavailability was estimated as 110 ± 11.5%. No clear trends in motility alteration were identified. No adverse effects were noted. Conclusions: Repeated SC boluses of metoclopramide at 0.08 mg/kg would result in lower total drug exposure and T than IV CRI administration but would be highly bioavailable. Conclusions: Higher and/or more frequent SC bolus doses are needed to achieve a similar AUC to IV CRI. No adverse effects were noted; however, evaluation of alternative dosing strategies is warranted.
© 2024 The Author(s). Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.
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Publication Date: 2024-06-24 PubMed ID: 38925540DOI: 10.1111/vsu.14128Google Scholar: Lookup
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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 the pharmacokinetics or how the body processes the drug metoclopramide in adult horses, and how this is affected by different methods of administration, and explores its effect on gastrointestinal motility and possible adverse side effects. It concludes that while subcutaneous administration of the drug resulted in lower overall exposure and duration, it was effectively absorbed into the body, with further research needed to determine optimized dosage strategies.

Research Design

  • This is an experimental study with a randomized, cross-over design, involving six healthy adult horses.
  • The horses were given metoclopramide via two methods – through a continuous rate infusion into the vein (IV CRI), and through a single dose injected under the skin (SC bolus).
  • There was a washout period of at least a week between the two treatments to ensure there was no carryover effect of the drug from the first treatment phase during the second treatment phase.
  • Plasma was analysed using Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). This is a highly sensitive technique used for plasma analysis.
  • They applied a method known as compartmental modeling to determine the pharmacokinetics parameters for each treatment and nonparametric superposition to model multiple SC bolus dosages.

Findings

  • The study found that the average time for the drug to peak in the body (T max) for SC bolus was significantly lower (0.583 hours) compared to IV CRI (17.3 hours).
  • Peak concentrations (C max) of the drug was also lower via SC bolus administration compared to the IV CRI method.
  • Area under the concentration time curve (AUC) which measures overall drug exposure, was lower with SC bolus administration compared to IV CRI, but would increase to similar levels as the IV CRI group at an overall daily dose of 0.96 mg/kg/day divided into three, four or six doses. SC bolus administration was estimated to be 110% bioavailable, meaning that it was completely absorbed by the body.
  • There were no clear trends in alteration of gastrointestinal motility, suggesting the drug had no significant influence on this.
  • No adverse side effects were noted in the research study.

Conclusions

  • The study concludes that for a similar drug exposure to the IV CRI method, the SC bolus method requires higher or more frequent doses. Even so, the drugs are suitably absorbed in the body when administered subcutaneously.
  • While the study found no adverse effects, the authors suggest further evaluation of alternative dosing strategies is needed to determine optimal dosages.

Cite This Article

APA
Brandon AM, Williams JM, Davis JL, Martin EG, Capper AM, Crabtree NE. (2024). Evaluation of pharmacokinetics of metoclopramide administered via subcutaneous bolus and intravenous constant rate infusion to adult horses. Vet Surg. https://doi.org/10.1111/vsu.14128

Publication

Veterinary surgery : VS
ISSN: 1532-950X
NlmUniqueID: 8113214
Country: United States
Language: English

Researcher Affiliations

Brandon, Amy M
  • Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA.
Williams, Jarred M
  • Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA.
Davis, Jen L
  • Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, Virginia, USA.
Martin, Emily G
  • Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, USA.
Capper, Ava M
  • Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA.
Crabtree, Naomi E
  • Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA.

Grant Funding

  • University of Georgia

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