FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Canadian journal of veterinary research = Revue canadienne de recherche veterinaire2016; 80(3); 230-235;

Pharmacokinetics of a combination of amikacin sulfate and penicillin G sodium for intravenous regional limb perfusion in adult horses.

Abstract: The aim of this study was to determine the pharmacokinetics of amikacin and penicillin G sodium when administered in combination as an intravenous regional limb perfusion (IVRLP) to horses. Seven healthy adult horses underwent an IVRLP in the cephalic vein with 2 g of amikacin sulfate and 10 mill IU of penicillin G sodium diluted to 60 mL in 0.9% saline. A pneumatic tourniquet set at 450 mmHg was left in place for 30 min. Synovial fluid was collected from the metacarpophalangeal joint 35 min and 2, 6, 12, and 24 h after infusion of the antimicrobials. Concentrations of amikacin and penicillin in synovial fluid were quantitated by liquid chromatography tandem-mass spectrometry analysis. Therapeutic concentrations of amikacin and penicillin for equine-susceptible pathogens were achieved in the synovial fluid. Maximum synovial concentrations (Cmax) (mean ± SE) for amikacin and penicillin were 132 ± 33 μg/mL and 8474 ± 5710 ng/mL, respectively. Only 3 horses had detectable levels of penicillin at 6 h and 1 at the 12 h sample. The combination of amikacin with penicillin G sodium via IVDLP resulted in reported therapeutic concentrations of both antibiotics in the synovial fluid. The Cmax:MIC (minimum inhibitory concentration) ratio for amikacin was 8:1 and Time > MIC for penicillin was 6 h. At 24 h, the mean concentration of amikacin was still above 4 μg/mL. Terminal elimination rate constants (T1/2 lambdaz) were 13.6 h and 2.8 h for amikacin and penicillin, respectively. The use of IVDLP with penicillin may therefore not be practical as rapid clearance of penicillin from the synovial fluid requires frequent perfusions to maintain acceptable therapeutic concentrations. L’objectif de la présente étude était de déterminer la pharmacocinétique de l’amikacine et de la pénicilline G sodique lorsqu’administrées en combinaison par perfusion intraveineuse régionale d’un membre (PIVRM) à des chevaux. Sept chevaux adultes ont reçu une PIVRM dans la veine céphalique avec 2 g de sulfate d’amikacine et 10 millions d’UI de pénicilline G sodique dilués dans 60 mL de saline 0,9 %. Un tourniquet pneumatique réglé à 450 mmHg a été laissé en place pour 30 min. Du liquide synovial a été récolté de l’articulation métacarpo-phalangienne 35 min, 2, 6, 12, et 24 h après l’infusion des antimicrobiens. Les concentrations d’amikacine et de pénicilline dans le liquide synovial furent mesurées par spectrométrie de masse en tandem avec la chromatographie en phase liquide. Les concentrations thérapeutiques d’amikacine et de pénicilline pour des agents pathogènes équins sensibles ont été atteintes dans le liquide synovial. Les concentrations synoviales maximales (Cmax) [moyenne ± écart-type (EC)] pour l’amikacine et la pénicilline étaient de 132 ± 33 μg/mL et 8474 ± 5710 ng/mL, respectivement. Seulement 3 chevaux avaient des quantités détectables de pénicilline à 6 h et un seul pour l’échantillon de 12 h. La combinaison d’amikacine et de pénicilline G sodique via PIVRM a permis de rapporter des concentrations thérapeutiques des deux antibiotiques dans le liquide synovial. Le ratio Cmax-CMI (concentration minimale inhibitrice) pour l’amikacine était de 8:1 et la période de Temps > CMI pour la pénicilline était de 6 h. À 24 h, la concentration moyenne d’amikacine était toujours supérieure à 4 μg/mL. Les constantes du taux d’élimination terminal (T1/2 lambdaz) étaient 13,6 h et 2,8 h pour l’amikacine et la pénicilline, respectivement. L’utilisation de PIVRM avec la pénicilline ne serait ainsi pas pratique étant donné que la clairance rapide de la pénicilline à partir du liquide synovial requière des perfusions fréquentes pour maintenir des concentrations thérapeutiques acceptables.(Traduit par Docteur Serge Messier).
Get Full Text
Publication Date: 2016-07-14 PubMed ID: 27408337PubMed Central: PMC4924558
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.
LinkedInCopy
  • 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.

This study evaluates the effectiveness of intravenous regional limb perfusion (IVRLP) therapy with a combined amikacin and penicillin in horses. It found that while this method achieved therapeutic levels of both antibiotics in the synovial fluid, rapid clearance of penicillin necessitates frequent perfusions to keep therapeutic concentrations.

Objective and Methodology of the Study

  • The research aimed to understand the pharmacokinetics ( how the body processes a drug) of amikacin and penicillin G sodium when administered through intravenous regional limb perfusion (IVRLP) in horses. IVRLP is a method used to deliver high concentrations of antibiotics directly to a localized area.
  • Seven healthy adult horses were used for the experiment where they were administered a combination of 2g amikacin sulfate and 10 million IU of penicillin G sodium via an IVRLP in their cephalic vein. A pneumatic tourniquet set at 450 mmHg was left in place for 30 min to restrict the spread of the drugs.
  • Samples of synovial fluid (fluid around the joints) were collected at specific intervals post the infusion to measure the antibiotic concentrations. The measuring was done using liquid chromatography tandem-mass spectrometry analysis.

Results of the Study

  • Therapeutic concentrations of amikacin and penicillin for pathogens susceptible to these antibiotics were achieved in the synovial fluid.
  • Maximum synovial concentrations (Cmax) for amikacin and penicillin were 132 ± 33 μg/mL and 8474 ± 5710 ng/mL, respectively.
  • Penicillin was detected in only three horses at the 6-hour mark, and in only one horse at the 12-hour sample collection.
  • The Cmax:MIC (minimum inhibitory concentration) ratio for amikacin was 8:1, hinting at its effective concentration. Time > MIC for penicillin was 6 hours, indicating that penicillin stayed at a therapeutic concentration for 6 hours.
  • Terminal elimination rate constants (indicating how long the drug stayed in system) were 13.6 hours for amikacin and 2.8 hours for penicillin.

Implications and Conclusion

  • The IVRLP method produced therapeutic concentrations of both amikacin and penicillin in the synovial fluid. Though this indicates the method’s effectiveness, penicillin’s rapid clearance from synovial fluid might necessitate frequent drug infusions to maintain its therapeutic concentration.
  • This could mean that the use of penicillin in IVRLP might be impractical due to the need for frequent infusions.
  • Therefore, the choice of antibiotic to be used in this kind of perfusion therapy might need to be reconsidered, especially for longer-term treatment.

Cite This Article

APA
Nieto JE, Trela J, Stanley SD, Yamout S, Snyder JR. (2016). Pharmacokinetics of a combination of amikacin sulfate and penicillin G sodium for intravenous regional limb perfusion in adult horses. Can J Vet Res, 80(3), 230-235.

Publication

Canadian journal of veterinary research = Revue canadienne de recherche veterinaire
ISSN: 1928-9022
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 80
Issue: 3
Pages: 230-235

Researcher Affiliations

Nieto, Jorge E
  • Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Trela, Jan
  • Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Stanley, Scott D
  • Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Yamout, Sawsan
  • Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Snyder, Jack R
  • Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.

MeSH Terms

  • Administration, Intravenous
  • Amikacin / administration & dosage
  • Amikacin / chemistry
  • Amikacin / pharmacokinetics
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Area Under Curve
  • Drug Therapy, Combination
  • Female
  • Half-Life
  • Horses / metabolism
  • Male
  • Penicillin G / administration & dosage
  • Penicillin G / chemistry
  • Penicillin G / pharmacokinetics
  • Perfusion / veterinary
  • Synovial Fluid / chemistry
  • Tissue Distribution

References

This article includes 40 references
  1. Cruz AM, Rubio-Martinez L, Dowling T. New antimicrobials, systemic distribution, and local methods of antimicrobial delivery in horses.. Vet Clin North Am Equine Pract 2006 Aug;22(2):297-322, vii-viii.
    pubmed: 16882477doi: 10.1016/j.cveq.2006.03.006google scholar: lookup
  2. Errico JA, Trumble TN, Bueno AC, Davis JL, Brown MP. Comparison of two indirect techniques for local delivery of a high dose of an antimicrobial in the distal portion of forelimbs of horses.. Am J Vet Res 2008 Mar;69(3):334-42.
    pubmed: 18312131doi: 10.2460/ajvr.69.3.334google scholar: lookup
  3. Kettner NU, Parker JE, Watrous BJ. Intraosseous regional perfusion for treatment of septic physitis in a two-week-old foal.. J Am Vet Med Assoc 2003 Feb 1;222(3):346-50, 316.
    pubmed: 12564599doi: 10.2460/javma.2003.222.346google scholar: lookup
  4. Lugo J, Gaughan EM. Septic arthritis, tenosynovitis, and infections of hoof structures.. Vet Clin North Am Equine Pract 2006 Aug;22(2):363-88, viii.
    pubmed: 16882480doi: 10.1016/j.cveq.2006.03.005google scholar: lookup
  5. Murphey ED, Santschi EM, Papich MG. Regional intravenous perfusion of the distal limb of horses with amikacin sulfate.. J Vet Pharmacol Ther 1999 Feb;22(1):68-71.
    pubmed: 10211721doi: 10.1046/j.1365-2885.1999.00180.xgoogle scholar: lookup
  6. Rubio-Martínez LM, Cruz AM. Antimicrobial regional limb perfusion in horses.. J Am Vet Med Assoc 2006 Mar 1;228(5):706-12, 655.
    pubmed: 16506931doi: 10.2460/javma.228.5.706google scholar: lookup
  7. Scheuch BC, Van Hoogmoed LM, Wilson WD, Snyder JR, MacDonald MH, Watson ZE, Steffey EP. Comparison of intraosseous or intravenous infusion for delivery of amikacin sulfate to the tibiotarsal joint of horses.. Am J Vet Res 2002 Mar;63(3):374-80.
    pubmed: 11911572doi: 10.2460/ajvr.2002.63.374google scholar: lookup
  8. Stewart AA, Goodrich LR, Byron CR, Evans RB, Stewart MC. Antimicrobial delivery by intrasynovial catheterisation with systemic administration for equine synovial trauma and sepsis.. Aust Vet J 2010 Apr;88(4):115-23.
    pubmed: 20402698doi: 10.1111/j.1751-0813.2010.00553.xgoogle scholar: lookup
  9. Whithair KJ, Bowersock TL, Blevins WE, Fessler JF, White MR, Van Sickle DC. Regional limb perfusion for antibiotic treatment of experimentally induced septic arthritis.. Vet Surg 1992 Sep-Oct;21(5):367-73.
    pubmed: 1413470doi: 10.1111/j.1532-950x.1992.tb01713.xgoogle scholar: lookup
  10. Schneider RK, Bramlage LR, Moore RM, Mecklenburg LM, Kohn CW, Gabel AA. A retrospective study of 192 horses affected with septic arthritis/tenosynovitis.. Equine Vet J 1992 Nov;24(6):436-42.
    pubmed: 1459056doi: 10.1111/j.2042-3306.1992.tb02873.xgoogle scholar: lookup
  11. Snyder JR, Pascoe JR, Hirsh DC. Antimicrobial susceptibility of microorganisms isolated from equine orthopedic patients.. Vet Surg 1987 May-Jun;16(3):197-201.
    pubmed: 3507142doi: 10.1111/j.1532-950x.1987.tb00938.xgoogle scholar: lookup
  12. Alkabes SB, Adams SB, Moore GE, Alkabes KC. Comparison of two tourniquets and determination of amikacin sulfate concentrations after metacarpophalangeal joint lavage performed simultaneously with intravenous regional limb perfusion in horses.. Am J Vet Res 2011 May;72(5):613-9.
    pubmed: 21529212doi: 10.2460/ajvr.72.5.613google scholar: lookup
  13. Mattson S, Bouré L, Pearce S, Hurtig M, Burger J, Black W. Intraosseous gentamicin perfusion of the distal metacarpus in standing horses.. Vet Surg 2004 Mar-Apr;33(2):180-6.
    pubmed: 15027980doi: 10.1111/j.1532-950x.2004.04026.xgoogle scholar: lookup
  14. Sole A, Nieto JE, Aristizabal FA, Snyder JR. Effect of emptying the vasculature before performing regional limb perfusion with amikacin in horses.. Equine Vet J 2016 Nov;48(6):737-740.
    pubmed: 26278891doi: 10.1111/evj.12501google scholar: lookup
  15. Zantingh AJ, Schwark WS, Fubini SL, Watts AE. Accumulation of amikacin in synovial fluid after regional limb perfusion of amikacin sulfate alone and in combination with ticarcillin/clavulanate in horses.. Vet Surg 2014 Mar;43(3):282-8.
    pubmed: 24467593doi: 10.1111/j.1532-950x.2014.12119.xgoogle scholar: lookup
  16. Palmer SE, Hogan PM. How to perform regional limb perfusion in the standing horse. Proceedings 45th Annu Conv Ann AAoc Equine Pract pp. 124–127.
  17. Santschi EM, Adams SB, Murphey ED. How to perform equine intravenous digital perfusion. 44th Annu Conv Am Assoc Equine Pract pp. 198–201.
  18. Wallace SM, Chan LY. In vitro interaction of aminoglycosides with beta-lactam penicillins.. Antimicrob Agents Chemother 1985 Aug;28(2):274-81.
    pmc: PMC180231pubmed: 3834833doi: 10.1128/aac.28.2.274google scholar: lookup
  19. Tindula RJ, Ambrose PJ, Harralson AF. Aminoglycoside inactivation by penicillins and cephalosporins and its impact on drug-level monitoring.. Drug Intell Clin Pharm 1983 Dec;17(12):906-8.
    pubmed: 6653408doi: 10.1177/106002808301701210google scholar: lookup
  20. Holt HA, Broughall JM, McCarthy M, Reeves DS. Interactions between aminoglycoside antibiotics and carbenicillin or ticarillin.. Infection 1976;4(2):107-9.
    pubmed: 7534doi: 10.1007/bf01638726google scholar: lookup
  21. Riff LJ, Thomason JL. Comparative aminoglycoside inactivation by beta-lactam antibiotics. Effects of a cephalosporin and six penicillins on five aminoglycosides.. J Antibiot (Tokyo) 1982 Jul;35(7):850-7.
    pubmed: 7174538doi: 10.7164/antibiotics.35.850google scholar: lookup
  22. Papich MG, Riviere JE. B-lactam antibiotics: Penicillins, cephalosporins, and related drugs. Veterinary Pharmacology & Therapeutics 9th ed. Vol. 1. United Sates: Wiley-Blackwell; 2009. pp. 865–893.
  23. Turnidge JD. The pharmacodynamics of beta-lactams.. Clin Infect Dis 1998 Jul;27(1):10-22.
    pubmed: 9675443doi: 10.1086/514622google scholar: lookup
  24. Mattson SE, Pearce SG, Bouré LP, Dobson H, Hurtig MB, Black WD. Comparison of intraosseous and intravenous infusion of technetium Tc 99m pertechnate in the distal portion of forelimbs in standing horses by use of scintigraphic imaging.. Am J Vet Res 2005 Jul;66(7):1267-72.
    pubmed: 16111168doi: 10.2460/ajvr.2005.66.1267google scholar: lookup
  25. Finsterbusch A, Argaman M, Sacks T. Bone and joint perfusion with antibiotics in the treatment of experimental staphylococcal infection in rabbits.. J Bone Joint Surg Am 1970 Oct;52(7):1424-32.
    pubmed: 5469195
  26. Moyer W, Schumacher J. A guide to equine joint injection and regional anesthesia. Yardley, OA: Veterinary Learning Systems; 2007.
  27. Uboh CE, Soma LR, Luo Y, McNamara E, Fennell MA, May L, Teleis DC, Rudy JA, Watson AO. Pharmacokinetics of penicillin G procaine versus penicillin G potassium and procaine hydrochloride in horses.. Am J Vet Res 2000 Jul;61(7):811-5.
    pubmed: 10895905doi: 10.2460/ajvr.2000.61.811google scholar: lookup
  28. Pinto N, Schumacher J, Taintor J, Degraves F, Duran S, Boothe D. Pharmacokinetics of amikacin in plasma and selected body fluids of healthy horses after a single intravenous dose.. Equine Vet J 2011 Jan;43(1):112-6.
    pubmed: 21143642doi: 10.1111/j.2042-3306.2010.00144.xgoogle scholar: lookup
  29. Lacy MK, Nicolau DP, Nightingale CH, Quintiliani R. The pharmacodynamics of aminoglycosides.. Clin Infect Dis 1998 Jul;27(1):23-7.
    pubmed: 9675444doi: 10.1086/514620google scholar: lookup
  30. Moore RD, Lietman PS, Smith CR. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration.. J Infect Dis 1987 Jan;155(1):93-9.
    pubmed: 3540140doi: 10.1093/infdis/155.1.93google scholar: lookup
  31. Zhanel GG, DeCorby M, Nichol KA, Wierzbowski A, Baudry PJ, Karlowsky JA, Lagacé-Wiens P, Walkty A, Mulvey MR, Hoban DJ. Antimicrobial susceptibility of 3931 organisms isolated from intensive care units in Canada: Canadian National Intensive Care Unit Study, 2005/2006.. Diagn Microbiol Infect Dis 2008 Sep;62(1):67-80.
    pubmed: 18513913doi: 10.1016/j.diagmicrobio.2008.04.012google scholar: lookup
  32. Isaksson B, Maller R, Nilsson LE, Nilsson M. Postantibiotic effect of aminoglycosides on staphylococci.. J Antimicrob Chemother 1993 Aug;32(2):215-22.
    pubmed: 8226423doi: 10.1093/jac/32.2.215google scholar: lookup
  33. Caron JP, Bolin CA, Hauptman JG, Johnston KA. Minimum inhibitory concentration and postantibiotic effect of amikacin for equine isolates of methicillin-resistant Staphylococcus aureus in vitro.. Vet Surg 2009 Jul;38(5):664-9.
    pubmed: 19573072doi: 10.1111/j.1532-950x.2009.00551.xgoogle scholar: lookup
  34. Kelmer G, Bell GC, Martin-Jimenez T, Saxton AM, Catasus C, Elliot SB, Meibohm B. Evaluation of regional limb perfusion with amikacin using the saphenous, cephalic, and palmar digital veins in standing horses.. J Vet Pharmacol Ther 2013 Jun;36(3):236-40.
    pubmed: 22607056doi: 10.1111/j.1365-2885.2012.01414.xgoogle scholar: lookup
  35. Stover SM, Brown MP, Kelly RH, Farver TB, Knight HD. Aqueous procaine penicillin G in the horse: serum, synovial, peritoneal, and urine concentrations after single-dose intramuscular administration.. Am J Vet Res 1981 Apr;42(4):629-31.
    pubmed: 7332124
  36. Cooke JV, Goldering D. The concentrations of penicillin in various body fluids during penicillin therapy. J Am Med Assoc 1945;127:80–87.
  37. Deshpande AD, Baheti KG, Chatterjee NR. Degradation of Beta-lactam antibiotics. Current Science 2004;87:1684–1695.
  38. Beccar-Varela AM, Epstein KL, White CL. Effect of experimentally induced synovitis on amikacin concentrations after intravenous regional limb perfusion.. Vet Surg 2011 Oct;40(7):891-7.
    pubmed: 22380674doi: 10.1111/j.1532-950x.2011.00875.xgoogle scholar: lookup
  39. Knottenbelt DC. Saunders Equine Frormulary. The Netherlands: Elsevier; 2006.
  40. Lescun TB, Vasey JR, Ward MP, Adams SB. Treatment with continuous intrasynovial antimicrobial infusion for septic synovitis in horses: 31 cases (2000-2003).. J Am Vet Med Assoc 2006 Jun 15;228(12):1922-9.
    pubmed: 16784387doi: 10.2460/javma.228.12.1922google scholar: lookup

Citations

This article has been cited 5 times.
  1. 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.
    doi: 10.3389/fvets.2021.629627pubmed: 33842571google scholar: lookup
  2. 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.
    doi: 10.1371/journal.pone.0221012pubmed: 31415623google scholar: lookup
  3. Dahan R, Oreff GL, Tatz AJ, Raz T, Britzi M, Kelmer G. Pharmacokinetics of regional limb perfusion using a combination of amikacin and penicillin in standing horses. Can Vet J 2019 Mar;60(3):294-299.
    pubmed: 30872853
  4. Guillot M, Mespoulhes-Rivière C, Bousquet-Mélou A, Lacroix MZ, Roques BB, Lallemand EA. Pharmacokinetics, pharmacodynamics, and local tolerance at injection site of penicillin and gentamicin administered by intravenous regional limb perfusion in standing horses: comparison between weightbearing and flexed limbs. BMC Vet Res 2025 Nov 7;21(1):650.
    doi: 10.1186/s12917-025-04936-0pubmed: 41204239google scholar: lookup
  5. Khatibzadeh SM, Dahlgren LA, Caswell CC, Ducker WA, Werre SR, Bogers SH. Equine bone marrow-derived mesenchymal stromal cells reduce established S. aureus and E. coli biofilm matrix in vitro. PLoS One 2024;19(10):e0312917.
    doi: 10.1371/journal.pone.0312917pubmed: 39480794google scholar: lookup
Subscribe to our newsletter
Join 99,727 horse owners like you who receive our email updates on horse health and nutrition.