Plasma and synovial fluid pharmacokinetics of a single intravenous dose of meropenem in adult horses.
Abstract: The objective of this study was to determine the pharmacokinetics of meropenem in horses after intravenous (IV) administration. A single IV dose of meropenem was administered to six adult horses at 10 mg/kg. Plasma and synovial fluid samples were collected for 6 hr following administration. Meropenem concentrations were determined by bioassay. Plasma and synovial fluid data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean ± SD values for elimination half-life, volume of distribution at steady-state, and clearance after IV administration for plasma samples were 0.78 ± 0.176 hr, 136.1 ± 19.69 ml/kg, and 165.2 ± 29.72 ml hr kg , respectively. Meropenem in synovial fluid had a slower elimination than plasma with a terminal half-life of 2.4 ± 1.16 hr. Plasma protein binding was estimated at 11%. Based on a 3-compartment open pharmacokinetic model of simultaneously fit plasma and synovial fluid, dosage simulations were performed. An intermittent dosage of meropenem at 5 mg/kg IV every 8 hr or a constant rate IV infusion at 0.5 mg/kg per hour should maintain adequate time above the MIC target of 1 μg/ml. Carbapenems are antibiotics of last resort in humans and should only be used in horses when no other antimicrobial would likely be effective.
© 2019 John Wiley & Sons Ltd.
Publication Date: 2019-06-20 PubMed ID: 31222751DOI: 10.1111/jvp.12770Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Clinical Trial
- Veterinary
- 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 is primarily concerned with the pharmacokinetics, which are the bodily processes affecting a drug, of meropenem in horses after being given intravenously. The team administered a single dose of the antibiotic to horses and tracked the levels of it in their plasma and synovial fluid.
Research Methodology
- The research involved six adult horses who were each administered with a single intravenous dose of meropenem at a dosage of 10mg/kg.
- For six hours after the administration, samples of plasma and synovial fluid were collected from the horses.
- The concentration levels of meropenem in the collected samples were then determined through a bioassay, which is a type of scientific experiment used to estimate the potency of substances.
- The acquired data from both the plasma and synovial fluid samples were analyzed using compartmental and noncompartmental pharmacokinetic methods. These are mathematical techniques used in pharmacokinetics to measure the time course of drug absorption, distribution, metabolism, and excretion.
Findings
- The plasma samples showed that the mean values for parameters such as elimination half-life, volume of distribution at steady-state, and clearance post IV administration came out to be 0.78 hours, 136.1ml/kg, and 165.2ml/hr kg respectively.
- The synovial fluid, on the other hand, displayed a slower elimination of meropenem with a terminal half-life of around 2.4 hours.
- It was estimated that the plasma protein binding, which is the degree to which medications attach to proteins within the blood, was approximately at 11%.
- The researchers also performed dosage simulations based on a 3-compartment open pharmacokinetic model of the simultaneously obtained plasma and synovial fluid.
- Using the results of these simulations, the team suggested that an intermittent dosage of 5 mg/kg IV every 8 hours or a constant rate IV infusion at 0.5 mg/kg per hour should be effective in maintaining time above the minimum inhibitory concentration (MIC) target of 1 μg/ml. The Minimum Inhibitory Concentration (MIC) is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation.
- Despite these findings, the research team stressed that carbapenems, a category of antibiotics which includes meropenem, should be reserved as a last resort treatment in horses, similar to their use in humans, and should only be implemented when it is unlikely that any other antimicrobial would prove effective.
Cite This Article
APA
Langston VC, Fontenot RL, Byers JA, Andrews CM, Mochal-King CA.
(2019).
Plasma and synovial fluid pharmacokinetics of a single intravenous dose of meropenem in adult horses.
J Vet Pharmacol Ther, 42(5), 525-529.
https://doi.org/10.1111/jvp.12770 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
MeSH Terms
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / chemistry
- Anti-Bacterial Agents / pharmacokinetics
- Area Under Curve
- Half-Life
- Horses / blood
- Meropenem / administration & dosage
- Meropenem / blood
- Meropenem / chemistry
- Meropenem / pharmacokinetics
- Synovial Fluid / chemistry
Grant Funding
- College of Veterinary Medicine, Mississippi State University
References
This article includes 11 references
- Albarellos GA, Montoya L, Passini SM, Lupi MP, Lorenzini PM, Landoni MF. Pharmacokinetics of meropenem after intravenous, intramuscular and subcutaneous administration to cats. Journal of Feline Medicine and Surgery 18(12), 976-980.
- Bidgood T, Papich MG. Plasma pharmacokinetics and tissue fluid concentrations of meropenem after intravenous and subcutaneous administration in dogs. American Journal of Veterinary Research 63(12), 1622-1628.
- Craig WA, Suh B. Protein binding and the antimicrobial effects: Methods for the determination of protein binding. In V. Lorian (Ed.),Antibiotics in laboratory medicine. 2ndedition. (pp. 477-514).Baltimore, MD: Williams & Wilkins.
- Dreetz M, Hamacher J, Eller J, Borner K, Koeppe P, Schaberg T, Lode H. Serum bactericidal activities and comparative pharmacokinetics of meropenem and imipenem-cilastatin. Antimicrobial Agents and Chemotherapy 40(1), 105-109.
- Fernández-Canigia L, Dowzicky MJ. Susceptibility of important Gram-negative pathogens to tigecycline and other antibiotics in Latin America between 2004 and 2010. Annals of Clinical Microbiology and Antimicrobials 11, 1-9.
- Fontenot RL, Langston VC, Zimmerman JA, Wills RW, Sloan PB, Mochal-King CA. Meropenem synovial fluid concentrations after intravenous regional limb perfusion in standing horses. Veterinary Surgery 47(6), 852-860.
- Howell A, Sutherland R, Rolinson GN. Effect of protein binding on levels of ampicillin and cloxacillin in synovial fluid. Clinical Pharmacology & Therapeutics 13(5 Part 1), 724-732.
- Nicolau DP. Pharmacokinetic and pharmacodynamic properties of meropenem. Clinical Infectious Diseases 47(S1), S32-S40.
- Orsini JA, Moate PJ, Boston RC, Norman T, Engiles J, Benson CE, Poppenga R. Pharmacokinetics of imipenem-cilastatin following intravenous administration in healthy adult horses. Journal of Veterinary Pharmacology and Therapeutics 28(4), 355-361.
- Pfizer Pharmaceuticals. (2006). MERREM ® I.V. Label. Retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050706s022lbl.pdf
- Thungrat K, Price SB, Carpenter DM, Boothe DM. Antimicrobial susceptibility patterns of clinical Escherichia coli isolates from dogs and cats in the United States: January 2008 through January 2013. Veterinary Microbiology 179(3-4), 287-295.
Citations
This article has been cited 3 times.- Totten KMC, Cunningham SA, Gades NM, Etzioni A, Patel R. Pharmacokinetic Assessment of Staphylococcal Phage K Following Parenteral and Intra-articular Administration in Rabbits. Front Pharmacol 2022;13:840165.
- Zhao Y, Zhu Y, Liu B, Mi J, Li N, Zhao W, Wu R, Holyoak GR, Li J, Liu D, Zeng S, Wang Y. Antimicrobial Susceptibility of Bacterial Isolates from Donkey Uterine Infections, 2018-2021. Vet Sci 2022 Feb 5;9(2).
- Mosichuk AP, Smith JS, Tatarniuk DM, Troy JR, Kreuder AJ. Meropenem Administered via Intravenous Regional Limb Perfusion for Orthopedic Sepsis in Horses: A Clinical Retrospective Study. Front Vet Sci 2021;8:629627.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
