The influence of age and dosage on the pharmacodynamics of dexmedetomidine in rabbits

Authors

  • Agnieszka Bienert Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poland
  • Włodzimierz Płotek Department of Teaching Anaesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Poland
  • Paweł Wiczling Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Poland
  • Justyna Warzybok Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poland
  • Katarzyna Borowska Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poland
  • Katarzyna Buda Department of Experimental Anaesthesiology, Poznan University of Medical Sciences, Poland
  • Karolina Kulińska Department of Experimental Anaesthesiology, Poznan University of Medical Sciences, Poland
  • Hanna Billert Department of Experimental Anaesthesiology, Poznan University of Medical Sciences, Poland
  • Roman Kaliszan Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Poland
  • Edmund Grześkowiak Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poland

DOI:

https://doi.org/10.20883/medical.e53

Keywords:

dexmedetomidine, rabbits, pedal withdrawal reflex

Abstract

Aim. This study aimed to examine the influence of maturation and dosage on the sedative and haemodynamic response observed in rabbits after the administration of dexmedetomidine.
Material and methods. The pharmacodynamics of dexmedetomidine was studied on 14 healthy New Zealand white rabbits at three periods of maturation; stage 1–1.5 months old, stage 2–2.5 months old and stage 3–6.5 months old ones. The administered dose of dexmedetomidine ranged from 25 µg/kg to 300 µg/kg of body weight. The pedal withdrawal reflex was used to measure the duration of anaesthesia. The heart rate and mean arterial pressure were measured at the third stage of the study to evaluate the haemodynamic response. A simple pharmacodynamic relationship between the dose and the duration of anesthesia was used to describe the data.
Results. We observed that young rabbits were less sensitive to dexmedetomidine than adult animals, as was reflected by the pedal withdrawal reflex, and we found that the haemodynamic response to dexmedetomidine depended on dosage of the drug. Dexmedetomidine decreased the mean blood pressure in a dosage-dependent manner with the highest decrease observed for the lowest dose. As the dose increased, the hypotensive effect of the drug was less noticeable. After the administration of dexmedetomidine the heart rate decreased to the same value regardless of the dose applied.

Downloads

Download data is not yet available.

References

Afshani N. Clinical application of dexmedetomidine. S Afr J Anaesthesiol Analg. 2010;16(3):50–6.

Jones CR. Perioperative uses of dexmedetomidine. Int Anesthesiol Clin. 2013;51(2):81–96.

Maldonado JR, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics. 2009;50(3):206–17.

Holliday SF, Kane-Gill SL, Empey PE, Buckley MS, Smith- burger PL. Interpatient variability in dexmedetomidine response: a survey of the literature. Scientific World Journal. 2014 Jan 16;2014:805013.

Tobias JD. Dexmedetomidine: applications in pediatric critical care and pediatric anesthesiology. Pediatr Crit Care Med. 2007;8(2):115–31.

De Cock RF, Piana C, Krekels EH, Danhof M, Allegaert K, Knibbe CA. The role of population PK-PD modelling in paediatric clinical research. Eur J Clin Pharmacol. 2011;67 Suppl 1:5–16.

Funk RS, Brown JT, Abdel-Rahman SM. Pediatric pharmacokinetics: human development and drug disposition.Pediatr Clin North Am. 2012;59(5):1001–16.

Petroz GC, Sikich N, James M, van Dyk H, Shafer SL, Schily M, Lerman J. A phase I Two-center Study of the Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Children. Anesthesiology. 2006;105:1098–110.

The European Regulation on medicines for paediatric use. Paediatr Respir Rev. 8(2):177–83.

Consultant PR (2006) EU paediatric regulation for testing medicines in children. http://www.child-medicines-research-info.com/paediatric-research-consultancy/eu-pae- diatric-regulation.asp. 23 June 2009.

Bienert A, Płotek W, Zawidzka I, Ratajczak N, Szczesny D, Wiczling P, et al. Influence of time of day on propofol pharmacokinetics and pharmacodynamics in rabbits. Chronobiol Int. 2011;28(4):318–29.

Bienert A, Płotek W, Wiczling P, Kostrzewski B, Kamińska A, Billert H, et al. The influence of the time of day on midazolam pharmacokinetics and pharmacodynamics in rabbits. Pharmacological Reports. 2014;66(1):143–52.

Adetunji A, Oguntoye CO, Esho VO. Evaluation of diazepam-ketamine-pentazocineanaesthesia in rabbits. Afr J Biomed Res. 2009;12(3):237–40.

Gibaldi M, Levy G. Dose-dependent decline of pharmacologic effects of drugs with linear pharmacokinetic characteristics, J Pharm Sci. 1972;61(4):567–9.

Bol CJ, Danhof M, Stanski DR, Mandema JW. Pharmacokinetic-pharmacodynamic characterization of the cardiovascular, hypnotic, EEG and ventilatory responses to dexmedetomidine in the rat. J Pharmacol Exp Ther. 1997;283(3):1051–8.

Kuusela E, Raekallio M, Anttila M, Falck I, Mölsä S, Vainio O. Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs. J Vet Pharmacol Ther. 2000;23(1):15–20.

Ansah OB, Raekallio M, Vainio O. Comparison of three doses of dexmedetomidine with medetomidine in cats following intramuscular administration. J Vet Pharmacol Ther. 1998;21(5):380–7.

Kuhmonen J, Pokorný J, Miettinen R, Haapalinna A, Jolkkonen J, Riekkinen P Sr. Neuroprotective effects of dexmedetomidine in the gerbil hippocampus after transient global ischemia. Anesthesiology. 1997;87(2):371–7.

Cosar M1, Eser O, Fidan H, Sahin O, Buyukbas S, Ela Y. The neuroprotective effect of dexmedetomidine in the hippocampus of rabbits after subarachnoid hemorrhage.Surg Neurol. 2009;71(1):54–9.

Zornow MH. Ventilatory, hemodynamic and sedative effects of the alpha 2 adrenergic agonist, dexmedetomidine. Neuropharmacology. 1991;30(10):1065–71.

Borkowski GL, Danneman PJ, Russell GB, Lang CM. An evaluation of three intravenous anesthetic regimens in New Zealand rabbits. Lab Anim Sci. 1990;40(3):270–6.

Varga M. Textbook of Rabbit Medicine. 2nd ed. BH Elsevier, Oxford 2003, 187.

Iirola T, Aantaa R, Laitio R, Kentala E, Lahtinen M, Wighton A, et al. Pharmacokinetics of prolonged infusion of high-dose dexmedetomidine in critically ill patients. Crit Care. 2011;15(5):R257.

Potts AL, Anderson BJ, Holford NH, Vu TC, Warman GR. Dexmedetomidine hemodynamics in children after cardiac surgery. Paediatr Anaesth. 2010;20(5):425–33.

Downloads

Published

2014-06-30

Issue

Section

Original Papers

How to Cite

1.
Bienert A, Płotek W, Wiczling P, Warzybok J, Borowska K, Buda K, et al. The influence of age and dosage on the pharmacodynamics of dexmedetomidine in rabbits. JMS [Internet]. 2014 Jun. 30 [cited 2024 Dec. 22];83(2):108-15. Available from: https://jms.ump.edu.pl/index.php/JMS/article/view/53