Recirculatory model of fentanyl disposition with the brain as the target organ

British Journal of Anaesthesia
Richard N UptonG L Ludbrook

Abstract

The factors affecting the concentrations of fentanyl in the brain after intravenous administration have not been completely quantified. A model integrating the role of brain, lung and systemic kinetics was developed based on data from conscious instrumented sheep. Brain 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. The best models of the lung and brain were incorporated into a recirculatory model of the whole-body disposition of fentanyl. The validity of the model structure was tested by its ability to describe published data on the effect of hypo-, normo- and hypercarbia on the blood and brain concentrations of fentanyl in anaesthetized dogs. The cerebral kinetics of fentanyl were consistent with partial membrane limitation: the time to 50% equilibration with arterial blood was 10.0 min. Lung kinetics had two distinct components: a shallow compartment that was 50% equilibrated with blood in 0.72 min, and a loss term probably representing sequestration. Despite its simplicity, the recirculatory model was an adequate description of the sheep data. The dog data could be described if cerebral blood ...Continue Reading

Citations

Aug 21, 2012·Journal of Pharmacokinetics and Pharmacodynamics·Richard N UptonLars Popper
Oct 27, 2012·Clinical Pharmacokinetics·Jörn LötschGerd Geisslinger
Jun 30, 2007·Clinical and Experimental Pharmacology & Physiology·Richard N Upton
Sep 22, 2010·Annual Review of Pharmacology and Toxicology·Malcolm RowlandGeoffrey Tucker
Nov 22, 2005·British Journal of Pharmacology·David J R FosterAllison Martinez
Aug 28, 2007·Anesthesiology·Michel M R F StruysSteven L Shafer
Jul 30, 2011·Expert Review of Neurotherapeutics·Mellar P Davis
Dec 13, 2018·Journal of Clinical Monitoring and Computing·Joseph RinehartMaxime Cannesson
Feb 2, 2006·British Journal of Anaesthesia·L M Ferguson, G B Drummond

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