title: Clinical effects and pharmacokinetic variables of romifidine and the peripheral α2-adrenoceptor antagonist MK-467 in horses.
abstract: OBJECTIVE
  To investigate the effects of MK-467 on sedation quality, and cardiopulmonary and pharmacokinetic variables in horses sedated intravenously (IV) with romifidine.
  
  
  METHODS
  Experimental, randomized, crossover design.
  
  
  METHODS
  Seven healthy mares.
  
  
  METHODS
  Romifidine (80 μg kg-1; R) and MK-467 (200 μg kg-1; MK) were administered IV alone and in combination (R + MK). Levels of sedation and borborygmi were scored. Heart rate (HR), direct arterial blood pressure (ABP) and respiratory rate (fR) were recorded. Arterial and venous blood gas analyses were performed and venous plasma drug concentrations were measured. Pharmacokinetic parameters were calculated. Linear mixed modelling for repeated measures, contrasts of least square means by Bonferroni correction tests, one-way anova for repeated measures with Bonferroni multiple comparison tests and paired Student's t-tests were used to compare results within and between treatments as appropriate. Significance was set at p < 0.05.
  
  
  RESULTS
  After R, ABP increased and HR and fRdecreased significantly. After R + MK, HR, fR, systolic and mean ABP decreased. MK alone increased both HR and fR. After R, ABP was significantly higher than after R + MK. HR and fRwere significantly higher after MK than after R and R + MK. Areas under the curve for sedation time were similar after R and R + MK. Intestinal activity decreased markedly after R and less after R + MK. Volume of distribution and clearance of romifidine were significantly higher and area under the concentration time curve extrapolated to infinity significantly lower after R + MK than after R.
  
  
  CONCLUSIONS
  Combined romifidine and MK-467 prevented the cardiovascular changes commonly seen with romifidine but did not affect sedation quality.
  
  
  CONCLUSIONS
  Combined IV romifidine and MK-467 can be used to attenuate the cardiovascular effects of romifidine, such as in horses with colic or undergoing general anaesthesia.
authors.affiliation: Davies Veterinary Specialists, Higham Gobion, UK. Marieke.devries@vetspecialists.co.uk.|Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland. Marieke.devries@vetspecialists.co.uk.
authors.forename: Annemarie
authors.initials: A
authors.lastname: de Vries
authors.affiliation: Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Soile Ae
authors.initials: SA
authors.lastname: Pakkanen
authors.affiliation: Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Marja R
authors.initials: MR
authors.lastname: Raekallio
authors.affiliation: College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA.
authors.forename: Abel
authors.initials: A
authors.lastname: Ekiri
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.|Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Scheinin
authors.affiliation: Taylor Monroe, Little Downham, UK.
authors.forename: Polly M
authors.initials: PM
authors.lastname: Taylor
authors.affiliation: Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Outi M
authors.initials: OM
authors.lastname: Vainio
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000493:pharmacokinetics* / Q000494:pharmacology; D000771:Anesthesia, Intravenous / Q000662:veterinary; D019162:Anesthetics, Combined; D000818:Animals; D001784:Blood Gas Analysis / Q000662:veterinary; D002319:Cardiovascular System / Q000187:drug effects; D018592:Cross-Over Studies; D054810:Deep Sedation / Q000662:veterinary; D005260:Female; D006736:Horses; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000494:pharmacology; D011807:Quinolizines / Q000493:pharmacokinetics* / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D019162:Anesthetics, Combined; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D011807:Quinolizines; C055732:vatinoxan; C076257:romifidine
keywords: MK-467; horses; peripheral antagonist; sedation; α2-agonist