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.
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.
KuKanich
Butch
B
Department of Molecular Biomedical Sciences, Pharmacology and Comparative Pain Research Laboratories, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Lascelles
B Duncan X
BD
Papich
Mark G
MG
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
D000701:Analgesics, Opioid; D009020:Morphine