Pharmacokinetics of amikacin in plasma and selected body fluids of healthy horses after a single intravenous dose.
Abstract: No studies have determined the pharmacokinetics of low-dose amikacin in the mature horse. Objective: To determine if a single i.v. dose of amikacin (10 mg/kg bwt) will reach therapeutic concentrations in plasma, synovial, peritoneal and interstitial fluid of mature horses (n=6). Methods: Drug concentrations of amikacin were measured across time in mature horses (n=6); plasma, synovial, peritoneal and interstitial fluid were collected after a single i.v. dose of amikacin (10 mg/kg bwt). Results: The mean±s.d. of selected parameters were: extrapolated plasma concentration of amikacin at time zero 144±21.8 µg/ml; extrapolated plasma concentration for the elimination phase 67.8±7.44 µg/ml, area under the curve 139±34.0 µg*h/ml, elimination half-life 1.34±0.408 h, total body clearance 1.25±0.281 ml/min/kg bwt; and mean residence time (MRT) 1.81±0.561 h. At 24 h, the plasma concentration of amikacin for all horses was below the minimum detectable concentration for the assay. Selected parameters in synovial and peritoneal fluid were maximum concentration (Cmax) 19.7±7.14 µg/ml and 21.4±4.39 µg/ml and time to maximum concentration 65±12.2 min and 115±12.2 min, respectively. Amikacin in the interstitial fluid reached a mean peak concentration of 12.7±5.34 µg/ml and after 24 h the mean concentration was 3.31±1.69 µg/ml. Based on a minimal inhibitory concentration (MIC) of 4 µg/ml, the mean Cmax:MIC ratio was 16.9±1.80 in plasma, 4.95±1.78 in synovial fluid, 5.36±1.10 in peritoneal fluid and 3.18±1.33 in interstitial fluid. Conclusions: Amikacin dosed at 10 mg/kg bwt i.v. once a day in mature horses is anticipated to be effective for treatment of infection caused by most Gram-negative bacteria. Conclusions: Low dose amikacin (10 mg/kg bwt) administered once a day in mature horses may be efficacious against susceptible microorganisms.
© 2010 EVJ Ltd.
Publication Date: 2010-08-23 PubMed ID: 21143642DOI: 10.1111/j.2042-3306.2010.00144.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study investigates how a single dose of the antibiotic amikacin is processed in the bodies of mature horses, tracking its concentrations across different bodily fluids. The aim is to explore the effectiveness of using low-dose amikacin for treating infections caused by most Gram-negative bacteria in horses.
Methodology
- The experiment focused on determining the pharmacokinetics – how the body absorbs, distributes, metabolizes, and excretes a drug – of amikacin in mature horses.
- Six healthy, mature horses were intravenously administered a single dose of amikacin (10 mg/kg of their body weight).
- After administration, the concentrations of amikacin were tracked over time in multiple body fluids; specifically, in plasma, synovial fluid (found in the joints), peritoneal fluid (found in the abdominal cavity), and interstitial fluid (surrounds the body’s cells).
Results
- Through the study, researchers found and tracked various pharmaceutical parameters such as concentrations at time zero, concentrations for the elimination phase, and area under the curve (a measure of the total drug exposure over time).
- The elimination half-life of the drug, which is the time it takes for half of the drug to be removed from the body, was approximately 1.34 hours.
- After 24 hours, the plasma concentration of amikacin for all participating horses was below the detectable limit for the assay (the testing method used).
- In synovial and peritoneal fluids, the maximum concentrations and the time taken to reach these concentrations were recorded. The concentration of amikacin in the interstitial fluid was also tracked.
- The study also examined the Cmax:MIC ratio, comparing the maximum concentration (Cmax) of amikacin in the body fluids to the minimum inhibitory concentration (MIC, the smallest concentration of the drug that prevents bacterial growth).
Conclusions
- The study suggested that a single intravenous dose of low-dose amikacin (10 mg/kg body weight), might be effective in treating infections caused by most Gram-negative bacteria in mature horses.
- The findings indicate that administering this dose once a day could be a viable treatment strategy for such infections.
Cite This Article
APA
Pinto N, Schumacher J, Taintor J, Degraves F, Duran S, Boothe D.
(2010).
Pharmacokinetics of amikacin in plasma and selected body fluids of healthy horses after a single intravenous dose.
Equine Vet J, 43(1), 112-116.
https://doi.org/10.1111/j.2042-3306.2010.00144.x Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Alabama, USA. nipinto@uga.edu
MeSH Terms
- Amikacin / administration & dosage
- Amikacin / analysis
- Amikacin / blood
- Amikacin / pharmacokinetics
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / analysis
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / pharmacokinetics
- Area Under Curve
- Ascitic Fluid / chemistry
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Extracellular Fluid / chemistry
- Half-Life
- Horses / blood
- Horses / metabolism
- Injections, Intravenous
- Synovial Fluid / chemistry
Citations
This article has been cited 8 times.- Gilbertie JM, Schnabel LV, Hickok NJ, Jacob ME, Conlon BP, Shapiro IM, Parvizi J, Schaer TP. Equine or porcine synovial fluid as a novel ex vivo model for the study of bacterial free-floating biofilms that form in human joint infections. PLoS One 2019;14(8):e0221012.
- Zhu Q, Gao X, Brown MD, Eismont F, Gu W. Effects of diurnal loading on the transport of charged antibiotics into intervertebral discs. J Biomech 2019 Apr 18;87:177-182.
- Zhu Q, Gao X, Li N, Gu W, Eismont F, Brown MD. Kinetics of charged antibiotic penetration into human intervertebral discs: A numerical study. J Biomech 2016 Sep 6;49(13):3079-3084.
- Nieto JE, Trela J, Stanley SD, Yamout S, Snyder JR. Pharmacokinetics of a combination of amikacin sulfate and penicillin G sodium for intravenous regional limb perfusion in adult horses. Can J Vet Res 2016 Jul;80(3):230-5.
- Rhodes DM, Magdesian KG, Byrne BA, Kass PH, Edman J, Spier SJ. Minimum inhibitory concentrations of equine Corynebacterium pseudotuberculosis isolates (1996-2012). J Vet Intern Med 2015 Jan;29(1):327-32.
- Motaghinasab S, Shirazi-Adl A, Parnianpour M, Urban JP. Disc size markedly influences concentration profiles of intravenously administered solutes in the intervertebral disc: a computational study on glucosamine as a model solute. Eur Spine J 2014 Apr;23(4):715-23.
- Nielsen MBD, Jørgensen AR, Stilling M, Mikkelsen MKD, Jørgensen NP, Bue M. Dynamic distribution of systemically administered antibiotics in orthopeadically relevant target tissues and settings. APMIS 2024 Dec;132(12):992-1025.
- Paegelow JL, Schoonover MJ, Young JM, Maxwell LK, Taylor JD, Gilliam LL, Holbrook TC. Pharmacokinetics of amikacin after intravenous, intra-articular, and combined intravenous and intra-articular administration in healthy neonatal foals. J Vet Intern Med 2024 May-Jun;38(3):1825-1834.
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