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Pharmacokinetics and pharmacodynamics of the myotoxic venom ofPseudechis australis(mulga snake) in the anesthetised rat
- Source :
- Clinical Toxicology. 52:604-610
- Publication Year :
- 2014
- Publisher :
- Informa UK Limited, 2014.
-
Abstract
- Myotoxicity is a common clinical effect of snake envenoming and results from either local or systemic myotoxins in snake venoms. Although numerous myotoxins have been isolated from snake venoms, there has been limited study on the relationship between the time course of venom concentrations (pharmacokinetics) and the time course of muscle injury measured as a rise in creatine kinase (CK) (pharmacodynamics).The aim of this study was to develop an in vivo model of myotoxicity to investigate the time course of myotoxicity and the effect of antivenom.Anesthetised rats were administered Pseudechis australis (mulga snake) venom either through i.v., i.m. or s.d. route, including a range of doses (5-100 μg/kg). Serial blood samples were collected for measurement of venom using enzyme immunoassay and measurement of CK and creatinine. Antivenom was administered before, 1 and 6 h after venom administration to investigate its effect on muscle injury. Plots of venom and CK versus time were made and the area under the curve (AUC) was calculated.There was a significant dose-dependent increase in CK concentration after administration of P. australis venom, which was greatest for i.v. administration. Timed measurement of venom concentrations showed a rapid absorption through s.d. and i.m. routes and a delayed rise in CK concentrations following any route. Antivenom prevented myotoxicity shown by a decrease in the CK AUC, which was most effective if given earliest. There was a rise in creatinine following i.v. venom administration.The study shows the delayed relationship between venom absorption and the rise in CK, consistent with the delayed onset of myotoxicity in human envenoming. Antivenom prevented myotoxicity more effectively if given earlier.
- Subjects :
- Male
Injections, Subcutaneous
Myotoxin
Antivenom
Venom
Context (language use)
Pharmacology
Toxicology
Injections, Intramuscular
complex mixtures
Immunoenzyme Techniques
Rats, Sprague-Dawley
Pharmacokinetics
Animals
Elapidae
Muscle, Skeletal
Pseudechis australis
Elapid Venoms
Dose-Response Relationship, Drug
biology
Creatine Kinase, MM Form
General Medicine
biology.organism_classification
Rats
Creatinine
Pharmacodynamics
Anesthesia
biology.protein
Creatine kinase
Subjects
Details
- ISSN :
- 15569519 and 15563650
- Volume :
- 52
- Database :
- OpenAIRE
- Journal :
- Clinical Toxicology
- Accession number :
- edsair.doi.dedup.....984009e2493e8257b5cd519326f03a38