Pharmacokinetic Interaction Between Indoramin and Ethanol

Abstract

<jats:p> 1 The effect of ethanol consumption (0.5 g/kg) on the pharmacokinetics of the alpha adrenoceptor antagonist indoramin, administered orally (50 mg) or intravenously (0.175 mg/kg) has been investigated in young volunteers. Sedation was also assessed using a visual analogue scale. </jats:p><jats:p> 2 After oral indoramin administration, ethanol caused increases of 58% (P &lt;0.01) in C<jats:sub>Pmax</jats:sub> , and 25% (P &lt;0.05) in AUC. There was no effect of alcohol on elimination half-life. The combination of ethanol and indoramin was more sedative than indoramin alone. </jats:p><jats:p> 3 Ethanol did not alter the pharmacokinetics of an intravenous dose of indoramin. However indoramin caused a small but statistically significant increase (26%) in blood ethanol concentrations during the first 1.25 h after dosing. Both indoramin and ethanol caused sedation. </jats:p><jats:p> 4 The increased bioavailability of oral indoramin in the presence of ethanol may reflect some enhanced absorption, but it is also consistent with inhibition of first-pass metabolism of a flow-limited drug. The clinical implications are discussed. </jats:p>