Document Detail

Cardiovascular and respiratory safety pharmacology in Göttingen minipigs: Pharmacological characterization.
MedLine Citation:
PMID:  21570473     Owner:  NLM     Status:  Publisher    
INTRODUCTION: 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 in tidal volume, respiratory rate and minute volume. DISCUSSION: 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.
S Authier; J Gervais; S Fournier; D Gauvin; S Maghezzi; E Troncy
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-3
Journal Detail:
Title:  Journal of pharmacological and toxicological methods     Volume:  -     ISSN:  1873-488X     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9206091     Medline TA:  J Pharmacol Toxicol Methods     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
LAB Research Inc., 445 Armand Frappier, Laval, Quebec, Canada H7V 4B3; GREPAQ, Department of Veterinary Biomedicine, Faculté de médecine vétérinaire, Université de Montréal, P.O. box 5000, St-Hyacinthe, Quebec, Canada J2S 7C6.
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