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Abstract
1. The haemodynamic effects and regional clearances of tocainide were investigated in sheep with chronic intravascular cannulae to measure blood flow through, and drug extraction by, lungs, kidneys, liver and gut.
2. Tocainide, at arterial blood concentrations in the therapeutic range, caused no haemodynamic effects and was significantly extracted only by the liver.
3. In the presence of general anaesthesia with halothane, the mean hepatic blood flow and tocainide extraction ratio were each reduced by approximately 25‰ so that the mean hepatic clearance and intrinsic clearance of tocainide each were reduced by approximately 50%. Thus arterial blood tocainide concentrations were increased by 50%.
4. While the clinical implications of this interaction are unclear because of insufficient information about the margin of safety of tocainide, the pharmacological implications are plain. Because general anaesthesia may alter the relationship between dose and blood drug concentrations, pharmacokinetic and pharmacodynamic data should not be interchanged between awake and anaesthetized subjects.