Pharmacokinetic interaction between indoramin and ethanol.
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. 2. After oral indoramin administration, ethanol caused increases of 58% (P less than 0.01) in Cpmax, and 25% (P less than 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. 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. 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.
Abrams
S M
SM
Department of Clinical Pharmacology, St Bartholomew's Hospital, London, UK.
Pierce
D M
DM
Johnston
A
A
Hedges
A
A
Franklin
R A
RA
Turner
P
P
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives; D007211:Indoles / Q000493:pharmacokinetics*; D007217:Indoramin / Q000493:pharmacokinetics* / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male
D006993:Hypnotics and Sedatives; D007211:Indoles; D007217:Indoramin; D000431:Ethanol