Drug metabolism and disposition : the biological fate of chemicals
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Drug Metab. Dispos. · Nov 1993
Comparative StudyDisposition of morphine and its 3- and 6-glucuronide metabolites during morphine infusion in the sheep.
A sheep preparation was used to examine the regional formation and extraction of morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), relative to the regional extraction of morphine, at four morphine dose rates. On separate occasions, four ewes received a 15-min loading infusion of morphine sulfate, followed by a constant infusion at 2.5, 5, 10, or 20 mg/hr for an additional 5.75 hr. During the 5th to 6th hr of infusion, blood samples were collected simultaneously from the aorta, pulmonary artery, hepatic vein, hepatic portal and renal veins, posterior vena cava, and coronary and sagittal sinuses. ⋯ The mean lambda for morphine, M3G, and M6G was 1.25 +/- 0.17, 0.80 +/- 0.03, and 0.82 +/- 0.09, respectively. The mean total body clearance of morphine with respect to blood was 1.58 +/- 0.27 liters/min. Mean (+/-SD) percentage urinary recoveries as morphine, M3G, and M6G were 14.7 +/- 8.5, 75.4 +/- 11.1, and 0.49 +/- 0.39, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)