title: Effects of group housing on ECG assessment in conscious cynomolgus monkeys.
abstract: BACKGROUND
  Assessing the cardiovascular safety of new chemical or biological entities is important during pre-clinical development. Electrocardiogram (ECG) assessments in non-human primate (NHP) toxicology studies are often made using non-invasive telemetry systems. We investigated whether ECG recording was feasible during group housing of NHPs, rather than the usual single housed arrangement, and whether it would impact the data collected or affect the ability to detect drug-induced changes in QTc interval.
  
  
  METHODS
  Following a period of acclimatisation to jackets, cynomolgus monkeys (3 males and 3 females) were housed in same sex groups of 3. Female monkeys were administered 4 doses of vehicle while male monkeys were administered vehicle, 15, 45, and 135mg/kg moxifloxacin. Each dose was administered on a separate dosing day. The same dosing protocol was repeated with the animals singly housed and the results from the two phases were compared including assessment of statistical power.
  
  
  RESULTS
  Heart rate (HR) was significantly lower, and PR and QT intervals were significantly higher, at multiple time points when the animals were group housed compared with the singly housed phase. QRS duration and QTc interval were less affected. Moxifloxacin increased QT and QTc intervals but had no consistent effect on HR, QRS duration or PR interval under group housed or singly housed conditions. Power analysis suggested that group housing did not adversely affect the magnitude of detectable changes of ECG parameters. In general, detection of slightly smaller changes was achieved under conditions of group housing.
  
  
  CONCLUSIONS
  The current study shows group housing to be technically possible during non-invasive ECG recording, resulting in lower resting heart rates and small improvements in sensitivity of detection of drug-induced effects. Given the psychological benefits of group housing for NHPs, it is a refinement that should be considered when conducting ECG assessments in NHP toxicology studies.
authors.affiliation: Center for Drug Safety Evaluation and Research (CDSER), State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Guozhen
authors.initials: G
authors.lastname: Xing
authors.affiliation: Center for Drug Safety Evaluation and Research (CDSER), State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Center for Drug Safety Evaluation and Research (CDSER), State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Hu
authors.affiliation: Center for Drug Safety Evaluation and Research (CDSER), State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Shaodong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Center for Drug Safety Evaluation and Research (CDSER), State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Center for Drug Safety Evaluation and Research (CDSER), State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Safety and Metabolism, AstraZeneca R&D, Mereside, Alderley Park, Macclesfield SK10 4TG, United Kingdom.
authors.forename: Jason
authors.initials: J
authors.lastname: Schofield
authors.affiliation: Discovery Sciences - Statistics, AstraZeneca R&D, Mereside, Alderley Park, Macclesfield SK10 4TG, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Oldman
authors.affiliation: Discovery Sciences - Statistics, AstraZeneca R&D, Mereside, Alderley Park, Macclesfield SK10 4TG, United Kingdom.
authors.forename: Debbie
authors.initials: D
authors.lastname: Adkins
authors.affiliation: Center for Drug Safety Evaluation and Research (CDSER), State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Safety and Metabolism, AstraZeneca R&D, Mereside, Alderley Park, Macclesfield SK10 4TG, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Platz
authors.affiliation: Center for Drug Safety Evaluation and Research (CDSER), State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: jren@cdser.simm.ac.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Safety and Metabolism, AstraZeneca R&D, Mereside, Alderley Park, Macclesfield SK10 4TG, United Kingdom. Electronic address: matthew.skinner@astrazeneca.com.
authors.forename: Matthew
authors.initials: M
authors.lastname: Skinner
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004562:Electrocardiography / Q000379:methods*; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000633:toxicity; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006799:Housing, Animal; D008133:Long QT Syndrome / Q000139:chemically induced / Q000175:diagnosis; D008252:Macaca fascicularis; D008297:Male; D000077266:Moxifloxacin; D013686:Telemetry / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods
chemical_list: D024841:Fluoroquinolones; D000077266:Moxifloxacin
keywords: Electrocardiogram; Group housing; Heart rate; Methods; Moxifloxacin; Non-human primate; Non-invasive telemetry; QT interval; Safety pharmacology; Single housing