A non-invasive and quantitative method for the study of tissue injury caused by intramuscular injection of drugs in horses.
Abstract: The present study was undertaken to measure the weight of muscle destroyed by an intramuscular injection of phenylbutazone (PBZ) in horses. In six horses, CK disposition parameters were evaluated after intravenous (i.v.) and intramuscular (i.m.) administration of a CK horse preparation. The same horses received PBZ, a potentially irritating agent, by i.v. and i.m. (neck and hindquarter) routes. Data were analysed using compartmental approaches and instantaneous CK flux was calculated using a discrete deconvolution method. For a 150 U/kg CK dose, the steady-state volume of distribution was 0.050 +/- 0.0115 L/kg and the plasma half-life was 112 +/- 18 min. After CK i.m. administration, the half-life of the terminal phase was 11.8 +/- 5.3 h indicating a flip-flop process and the mean bioavailability of CK was close to 100%. After PBZ i.m. administration, the CK activity was significantly increased with peak values of 508 +/- 109 U/L after the neck administration and 873 +/- 365 U/L after the gluteal administration. By measuring the total amount of CK released from injured muscle, it was calculated that an equivalent of 0.044 +/- 0.029 g/kg of muscle was destroyed after PBZ administration in the neck. The corresponding figure was 0.118 +/- 0.048 g/kg after intragluteal PBZ administration. By deconvoluting plasma CK activity, it was shown that the CK entry rate was maximum for the first 30-60 min following PBZ administration, which then decreased slowly to return to the control value after a delay of 24-48 h after PBZ administration. It was concluded that the CK release pattern following a controlled muscular damage was a non-invasive approach useful for quantifying the amount of damaged muscle, and that the calculation of CK input rate by deconvolution was of potential interest in describing events at the muscle cell level.
Publication Date: 1995-06-01 PubMed ID: 7674460DOI: 10.1111/j.1365-2885.1995.tb00583.xGoogle Scholar: Lookup
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- Journal Article
- Biochemistry
- Biological Half-Life
- Clinical Pathology
- Clinical Study
- Creatine Kinase
- Diagnostic Technique
- Equine Diseases
- Equine Health
- Horses
- Injury
- Intramuscular Administration
- Musculoskeletal System
- Noninvasive Procedures
- Pharmacokinetics
- Pharmacology
- Phenylbutazone
- Physiology
- Tissue
- Veterinary Medicine
- Veterinary Research
Summary
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The research is about a non-invasive way to quantify tissue damage in horses caused by intramuscular injections, using phenylbutazone as the injecting agent. It provides a method to measure the weight of muscle destroyed after injections, utilizing the creatine kinase (CK) disposition parameters.
Study Design & Methods
- The experiment was performed on six horses using intravenous and intramuscular administration of a creatine kinase (CK) horse preparation. This CK preparation was specific to horses and used to measure the CK release pattern after a controlled muscle injury.
- Phenylbutazone (PBZ), a potentially irritating substance, was administered via intravenous and intramuscular pathways, specifically targeting the neck and hindquarter areas.
- Data collected was analysed with compartmental models, and the instantaneous CK flux was calculated using a discrete deconvolution method. This method was used to analyse and interpret the data as it helped to understand the maximum CK entry rate after the administration of PBZ, providing a clearer picture of the extent of muscle damage.
Results
- For a CK dose of 150 U/kg, the results showed that the steady-state volume distribution was 0.050 +/- 0.0115 L/kg and the plasma half-life was 112 +/- 18 mins.
- The terminal phase half-life after CK intramuscular administration was 11.8 +/- 5.3 hours. It was observed that there was a flip-flop process indicating that the CK absorption rate was less than the elimination rate.
- The bioavailability of CK was close to 100% after intramuscular administration.
- The CK activity significantly increased after PBZ intramuscular administration, with peak values after neck and gluteal injections.
- By measuring the total CK released from injured muscle, they calculated that the equivalent of 0.044 +/- 0.029 g/kg of muscle was destroyed following PBZ administration in the neck and 0.118 +/- 0.048 g/kg after intragluteal PBZ administration.
Conclusions
- The research concluded that observing the CK release pattern after muscular damage provides a non-invasive approach to quantifying muscle damage in horses.
- The calculation of CK input rate by deconvolution has potential interest in describing events at the muscle cell level post PBZ administration.
- The research presents a viable means to quantify tissue injury following an intramuscular injection, which might provide a safer approach to drug administration in horses in the future.
Cite This Article
APA
Toutain PL, Lassourd V, Costes G, Alvinerie M, Bret L, Lefebvre HP, Braun JP.
(1995).
A non-invasive and quantitative method for the study of tissue injury caused by intramuscular injection of drugs in horses.
J Vet Pharmacol Ther, 18(3), 226-235.
https://doi.org/10.1111/j.1365-2885.1995.tb00583.x Publication
Researcher Affiliations
- Ecole Nationale Vétérinaire de Toulouse, Département de Physiopathologie, France.
MeSH Terms
- Animals
- Biological Availability
- Creatine Kinase / analysis
- Creatine Kinase / metabolism
- Creatine Kinase / pharmacokinetics
- Cross-Over Studies
- Half-Life
- Horses / injuries
- Injections, Intramuscular / adverse effects
- Injections, Intramuscular / veterinary
- Injections, Intravenous / veterinary
- Muscle, Skeletal / drug effects
- Muscle, Skeletal / enzymology
- Muscle, Skeletal / injuries
- Phenylbutazone / administration & dosage
- Phenylbutazone / adverse effects
- Phenylbutazone / pharmacokinetics
Citations
This article has been cited 5 times.- Jahn P, Dobešová D, Brumarová R, Tóthová K, Kopecká A, Friedecký D. Dynamics of acylcarnitines, hypoglycin A, méthylènecyclopropylglycine and their metabolites in a Kladruber stallion with atypical myopathy. Vet Q 2022 Dec;42(1):183-191.
- Yáñez JA, Remsberg CM, Sayre CL, Forrest ML, Davies NM. Flip-flop pharmacokinetics--delivering a reversal of disposition: challenges and opportunities during drug development. Ther Deliv 2011 May;2(5):643-72.
- Pyörälä S, Laurila T, Lehtonen S, Leppä S, Kaartinen L. Local tissue damage in cows after intramuscular administration of preparations containing phenylbutazone, flunixin, ketoprofen and metamizole. Acta Vet Scand 1999;40(2):145-50.
- Barrantes Murillo DF, Cattley RC, Cullen JM, Withers C, Towns J, Pfeifle R, Wooldridge A, Neto RLALT. Intrahepatic mucinous cholangiocarcinoma with recurrent colic in a horse case report and literature review of cholangiocarcinoma in horses. J Vet Diagn Invest 2024 Jul;36(4):547-553.
- Aroch I, Keidar I, Himelstein A, Schechter M, Shamir MH, Segev G. Diagnostic and prognostic value of serum creatine-kinase activity in ill cats: a retrospective study of 601 cases. J Feline Med Surg 2010 Jun;12(6):466-75.
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