RT Journal Article
SR Electronic
T1 Influence of Renal Failure on the Disposition of Morphine, Morphine-3-Glucuronide and Morphine-6-Glucuronide in Sheep during Intravenous Infusion with Morphine
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 779
OP 786
VO 282
IS 2
A1 Robert W. Milne
A1 Colin F. McLean
A1 Laurence E. Mather
A1 Roger L. Nation
A1 William B. Runciman
A1 Albert J. Rutten
A1 Andrew A. Somogyi
YR 1997
UL http://jpet.aspetjournals.org/content/282/2/779.abstract
AB The influence of experimentally induced renal failure on the disposition of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) was examined in seven sheep infused intravenously with morphine for 6 hr. Between 5 and 6 hr, blood was collected from the aorta, pulmonary artery, hepatic, hepatic portal and renal veins and posterior vena cava. Additional samples from the aorta and urine were collected up to 144 hr. Morphine, M3G and M6G were determined in plasma and urine by high-performance liquid chromatography. Constant concentrations of morphine, but not of M3G and M6G, were achieved in plasma between 5 and 6 hr. Significant (P < .001) extraction of morphine by the liver (0.72 ± 0.05) and kidney (0.42 ± 0.15) occurred. Compared with sheep with normal kidneys (Milne et al., 1995), renal failure did not alter (P = .11) the mean total clearance of morphine (1.5 ± 0.3 liters/min); clearance by the kidney was less (P < .001). However, a paired comparison using sheep common to this study and from the study when their kidneys were normal revealed a significant reduction in mean total clearance of 25%. The renal extraction of M3G and M6G and urinary recovery of the dose as summed morphine, M3G and M6G were reduced by renal failure. The kidney metabolized morphine to M3G. The data suggest that nonrenal elimination of M3G becomes more important during renal failure. The American Society for Pharmacology and Experimental Therapeutics