title: Cardiovascular and respiratory safety pharmacology in Göttingen minipigs: Pharmacological characterization.
abstract: BACKGROUND
  Similarities between pigs and humans support the relevance of Göttingen minipigs for regulatory safety pharmacology. The minipig is the species of choice for cardiovascular safety pharmacology when pivotal repeat toxicology studies are conducted in this species.
  
  
  METHODS
  4 male Göttingen minipigs with cardiovascular telemetry transmitters received intravenous saline, esmolol (0.5, 1, 2, 4 and 8mg/kg), medetomidine (0.04mg/kg), remifentanil (0.5, 1, 2, 4, 8 and 16μg/kg) and dopamine (2, 8, 10, 20, 30 and 50μg/kg/min) and oral sotalol (3 and 10mg/kg). Respiratory monitoring was conducted in 3 male and 3 female Göttingen minipigs receiving intravenous saline and methacholine (0, 3.4, 13.5 and 68μg/kg).
  
  
  RESULTS
  Heart rate (HR) corrected QT was optimal with a method based on analysis of covariance (QTca) followed by Fridericia's standard formula. Esmolol induced a decrease in HR. Medetomidine was associated with an initial hypertension with bradycardia followed by sustained hypotension, bradycadia and prolonged QTc. Remifentanil induced a dose-dependent QTc shortening with an increase in arterial pressures. Sotalol caused a decrease in HR and systolic arterial pressure with an increase in PR and QTc intervals. Dopamine induced an increase in arterial and pulse pressures. Methacholine increased tidal volume, respiratory rate and minute volume.
  
  
  CONCLUSIONS
  The results suggest that the minipig is a valid alternative to other non-rodent species for cardiovascular and respiratory safety pharmacology studies when this species is justified.
authors.affiliation: LAB Research North America, 445 Armand Frappier, Laval, Quebec, Canada H7V 4B3. authiers@labresearch.com
authors.forename: S
authors.initials: S
authors.lastname: Authier
authors.forename: J
authors.initials: J
authors.lastname: Gervais
authors.forename: S
authors.initials: S
authors.lastname: Fournier
authors.forename: D
authors.initials: D
authors.lastname: Gauvin
authors.forename: S
authors.initials: S
authors.lastname: Maghezzi
authors.forename: E
authors.initials: E
authors.lastname: Troncy
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004298:Dopamine / Q000494:pharmacology / Q000633:toxicity; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography / Q000187:drug effects / Q000662:veterinary; D005260:Female; D006339:Heart Rate; D008297:Male; D020926:Medetomidine / Q000494:pharmacology / Q000633:toxicity; D023421:Models, Animal; D010880:Piperidines / Q000494:pharmacology / Q000633:toxicity; D011412:Propanolamines / Q000494:pharmacology / Q000633:toxicity; D000077208:Remifentanil; D012137:Respiratory System / Q000187:drug effects*; D013015:Sotalol / Q000494:pharmacology / Q000633:toxicity; D013552:Swine; D013556:Swine, Miniature; D013686:Telemetry / Q000379:methods; D018675:Toxicity Tests / Q000379:methods
chemical_list: D010880:Piperidines; D011412:Propanolamines; D013015:Sotalol; C036604:esmolol; D020926:Medetomidine; D000077208:Remifentanil; D004298:Dopamine