title: Use of a von Frey device for evaluation of pharmacokinetics and pharmacodynamics of morphine after intravenous administration as an infusion or multiple doses in dogs.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics and pharmacodynamics of morphine after IV administration as an infusion or multiple doses in dogs by use of a von Frey (vF) device.
  
  
  METHODS
  6 dogs.
  
  
  METHODS
  In the first 2 crossover experiments of a 3-way crossover study, morphine or saline (0.9%) solution was administered via IV infusion. Loading doses and infusion rates were administered to attain targeted plasma concentrations of 10, 20, 30, and 40 ng/mL. In the third experiment, morphine (0.5 mg/kg) was administered IV every 2 hours for 3 doses. The vF thresholds were measured hourly for 8 hours. Plasma concentrations of morphine were measured by high-pressure liquid chromatography.
  
  
  RESULTS
  No significant changes in vF thresholds were observed during infusion of saline solution. The vF thresholds were significantly increased from 5 to 8 hours during the infusion phase, corresponding to targeted morphine plasma concentrations > 30 ng/mL and infusion rates > or = 0.15 +/- 0.02 mg/kg/h. The maximal effect (EMAX) was 78 +/- 11% (percentage change from baseline), and the effective concentration to attain a 50% maximal response (EC50) was 29.5 +/- 5.4 ng/mL. The vF thresholds were significantly increased from 1 to 7 hours during the multiple-dose phase; the EC50 and EMAX were 23.9 +/- 4.7 ng/mL and 173 +/- 58%, respectively. No significant differences in half-life, volume of distribution, or clearance between the first and last dose of morphine were detected.
  
  
  CONCLUSIONS
  Morphine administered via IV infusion (0.15 +/- 0.02 mg/kg/h) and multiple doses (0.5 mg/kg, IV, every 2 hours for 3 doses) maintained significant antinociception in dogs.
authors.affiliation: Department of Molecular Biomedical Sciences, Pharmacology and Comparative Pain Research Laboratories, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
authors.forename: Butch
authors.initials: B
authors.lastname: KuKanich
authors.forename: B Duncan X
authors.initials: BD
authors.lastname: Lascelles
authors.forename: Mark G
authors.initials: MG
authors.lastname: Papich
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D018592:Cross-Over Studies; D004285:Dogs / Q000097:blood*; D005260:Female; D006207:Half-Life; D006400:Hematocrit / Q000662:veterinary; D007262:Infusions, Intravenous / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D010147:Pain Measurement / Q000662:veterinary; D011897:Random Allocation; D018709:Statistics, Nonparametric
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine