PMID: 12765891May 27, 2003Paper

Cerebral and lung kinetics of morphine in conscious sheep after short intravenous infusions

British Journal of Anaesthesia
Richard N UptonR W Milne

Abstract

The analgesic effects of morphine are delayed relative to its concentration in blood. The rate of equilibration of morphine between blood and brain may contribute to this delay, but the kinetics of this process have not been modelled. This was determined in conscious instrumented sheep. The lung kinetics of morphine were also determined given their importance in defining systemic kinetics after i.v. bolus administration. Sheep were given short i.v. infusions of morphine (30 mg over 4 min). Cerebral kinetics were inferred from arterio-sagittal sinus concentration gradients and cerebral blood flow, and lung kinetics from the pulmonary artery-aortic gradient and cardiac output. These data were fitted to flow- and membrane-limited models of the kinetics in each organ. Morphine had minimal cardiovascular effects, did not alter cerebral blood flow and caused insignificant respiratory depression. Lung kinetics were best described by a single distribution volume (2036 ml) with a first-order loss (1370 ml min(-1)), which was attributed to deep distribution. The cerebral kinetics of morphine were characterized by a significant permeability barrier. Permeability across the barrier (7.44 ml min(-1)) was estimated with good precision, and w...Continue Reading

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Citations

Nov 15, 2005·Journal of Pharmacokinetics and Pharmacodynamics·David J R FosterAllison Martinez
Jan 10, 2009·World Journal of Gastroenterology : WJG·Anne Estrup OlesenRichard N Upton
Oct 1, 2010·Therapeutic Delivery·Joseph A Nicolazzo, Dharmini C Mehta
May 27, 2006·Journal of Pharmaceutical Sciences·Hanne H VillesenCliff Grant
Apr 25, 2007·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·M L JensenA Somogyi
Nov 22, 2005·British Journal of Pharmacology·David J R FosterAllison Martinez
Oct 4, 2006·British Journal of Pharmacology·H H VillesenC Grant
Dec 2, 2004·Peptides·Richard J Bodnar, Gad E Klein
May 1, 2021·Animals : an Open Access Journal From MDPI·Alison SmallIan Colditz

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