title: Pharmacokinetics and pharmacodynamics of intravenous romifidine and propranolol administered alone or in combination for equine sedation.
abstract: OBJECTIVE
  Propranolol has been suggested for anxiolysis in horses, but its sedation efficacy and side effects, both when administered alone and in combination with α2-adrenoceptor agonists, remain undetermined. This study aimed to document the pharmacokinetics and pharmacodynamics of propranolol, romifidine and their combination.
  
  
  METHODS
  Randomized, crossover study.
  
  
  METHODS
  Six adult horses weighing 561 ± 48 kg.
  
  
  METHODS
  Propranolol (1 mg kg-1; treatment P), romifidine (0.1 mg kg-1; treatment R) or their combination (treatment PR) were administered intravenously with a minimum of 1 week between treatments. Alertness, behavioral responsiveness (visual and tactile) and physiologic variables were measured before and up to 960 minutes after drug administration. Blood was collected for blood gas and acid-base analyses and measurement of plasma drug concentrations. Data were analyzed using repeated-measures analysis of variance or Friedman with Holm-Sidak and Wilcoxon rank-sum tests (p < 0.05).
  
  
  RESULTS
  Systemic clearance significantly decreased and the area under the concentration-time curve significantly increased for both drugs in PR compared with P and R. Both PR and R decreased behavioral responsiveness and resulted in sedation for up to 240 and 480 minutes, respectively. Sedation was deeper in PR for the first 16 minutes. Heart rate significantly decreased in all treatments for at least 60 minutes, and PR significantly increased the incidence of severe bradycardia (<20 beats minute-1).
  
  
  CONCLUSIONS
  Although not associated with reduced behavioral responsiveness or sedation alone, propranolol augmented romifidine sedation, probably through alterations in romifidine pharmacokinetics, in horses administered PR. The occurrence of severe bradycardia warrants caution in the co-administration of these drugs at the doses studied.
authors.affiliation: Veterinary Medical Teaching Hospital, University of California Davis, Davis, CA, USA.
authors.forename: Alessia
authors.initials: A
authors.lastname: Cenani
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA. Electronic address: rjbrosnan@ucdavis.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Brosnan
authors.affiliation: Department of Animal Science, University of California Davis, Davis, CA, USA.
authors.forename: Shara
authors.initials: S
authors.lastname: Madigan
authors.affiliation: KL Maddy Equine Analytical Chemistry Laboratory, University of California Davis, Davis, CA, USA.
authors.forename: Heather K
authors.initials: HK
authors.lastname: Knych
authors.affiliation: Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Madigan
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced / Q000662:veterinary; D018592:Cross-Over Studies; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006734:Horse Diseases / Q000139:chemically induced; D006736:Horses; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D011433:Propranolol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D018686:Anesthetics, Intravenous; D007093:Imidazoles; C076257:romifidine; D011433:Propranolol
keywords: bradycardia; equine; propranolol. romifidine; sedation