Pharmacokinetics of morphine and plasma concentrations of morphine-6-glucuronide following morphine administration to dogs.
The purpose of this study was to evaluate the pharmacokinetics of morphine and morphine-6-glucuronide (M-6-G) following morphine administered intravenously and orally to dogs in a randomized crossover design. Six healthy 3-4-year-old Beagle dogs were administered morphine sulfate (0.5 mg/kg) as an i.v. bolus and extended release tablets were administered orally as whole tablets (1.6 +/- 0.1 mg/kg) in a randomized crossover design. Plasma concentrations of morphine and M-6-G were determined using high-pressure liquid chromatography and electrochemical coulometric detection. Following i.v. administration all dogs exhibited dysphoria and sedation, and four or six dogs vomited. Mean +/- SE values for half-life, apparent volume of distribution, and clearance after i.v. administration were 1.16 +/- 0.15 h, 4.55 +/- 0.17 L/kg, and 62.46 +/- 10.44 mL/min/kg, respectively. One dog vomited following oral administration and was excluded from the oral analysis. Oral bioavailability was 5% as determined from naïve-averaged analysis. The M-6-G was not detected in any plasma samples following oral or i.v. administration of morphine at a 25 ng/mL the limit of quantification. Computer simulations concluded morphine sulfate administered 0.5 mg/kg intravenously every 2 h would maintain morphine plasma concentrations consistent with analgesic plasma concentrations in humans. Oral morphine is poorly and erratically absorbed in dogs.
KuKanich
B
B
Department of Molecular Biomedical Sciences, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC, USA. Butch_Kukanich@yahoo.com
Lascelles
B D X
BD
Papich
M G
MG
D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004285:Dogs / Q000378:metabolism*; D005260:Female; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000097:blood*
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine