title: Pharmacokinetics, pharmacodynamics, and analgesic effects of morphine after rectal, intramuscular, and intravenous administration in dogs.
abstract: OBJECTIVE
  To compare systemic bioavailability and duration for therapeutic plasma concentrations and cardiovascular, respiratory, and analgesic effects of morphine administered per rectum, compared with IV and IM administration in dogs.
  
  
  METHODS
  6 healthy Beagles.
  
  
  METHODS
  In a randomized study, each dog received the following: morphine IV (0.5 mg/kg of body weight), morphine per rectum (1, 2, and 5 mg/kg as a suppository and 2 mg/kg as a solution), and a control treatment. Intramuscular administration of morphine (1 mg/kg) was evaluated separately. Heart and respiratory rates, systolic, diastolic, and mean blood pressures, adverse effects, and plasma morphine concentrations were measured. Analgesia was defined as an increase in response threshold, compared with baseline values, to applications of noxious mechanical (pressure) and thermal (heat) stimuli. Data were evaluated, using Friedman repeated-measures ANOVA on ranks and Student-Newman-Keuls post-hoc t-tests.
  
  
  RESULTS
  Significant differences were not found in cardiovascular, respiratory, or analgesia values between control and morphine groups. Overall systemic bioavailability of morphine administered per rectum was 19.6%. Plasma morphine concentration after administration of the highest dose (5 mg/kg) as a suppository was significantly higher than concentrations 60 and 360 minutes after IV and IM administration, respectively. A single route of administration did not consistently fulfill our criteria for providing analgesia.
  
  
  CONCLUSIONS
  Rectal administration of morphine did not increase bioavailability above that reported for oral administration of morphine in dogs. Low bioavailability and plasma concentrations limit the clinical usefulness of morphine administered per rectum in dogs.
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus 43210, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Barnhart
authors.forename: J A
authors.initials: JA
authors.lastname: Hubbell
authors.forename: W W
authors.initials: WW
authors.lastname: Muir
authors.forename: R A
authors.initials: RA
authors.lastname: Sams
authors.forename: R M
authors.initials: RM
authors.lastname: Bednarski
mesh_terms: D000285:Administration, Rectal; D000698:Analgesia / Q000662:veterinary*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006339:Heart Rate / Q000187:drug effects; D006358:Hot Temperature; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D010146:Pain / Q000517:prevention & control / Q000662:veterinary*; D011312:Pressure; D011897:Random Allocation
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine