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Pharmacokinetics of morphine and plasma concentrations of morphine‐6‐glucuronide following morphine administration to dogs
Author(s) -
KUKANICH B.,
LASCELLES B. D. X.,
PAPICH M. G.
Publication year - 2005
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2005.00661.x
Subject(s) - morphine , pharmacokinetics , crossover study , bioavailability , beagle , volume of distribution , pharmacology , chemistry , oral administration , sedation , analgesic , bolus (digestion) , anesthesia , medicine , alternative medicine , pathology , placebo
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.