The pharmacokinetics of indoramin and 6-hydroxyindoramin in poor and extensive hydroxylators of debrisoquine

European Journal of Clinical Pharmacology
D M PierceR A Franklin


Five poor metabolisers (PM) and seven extensive metabolisers (EM), of debrisoquine, all healthy volunteers, received 50 mg indoramin orally following an overnight fast. Plasma concentrations of indoramin and 6-hydroxyindoramin were determined by HPLC with fluorimetric detection. In PM subjects, mean values of Cmax (158 ng/ml) and AUC(0-24) (2556 ng X h X m-1) for indoramin were substantially elevated and t 1/2 beta (18.5 h) prolonged by comparison with values in the EM subjects (21.6 ng/ml, 151 ng X h X ml-1 and 5.2 h respectively). For 6-hydroxyindoramin, on the other hand, Cmax (12.4 ng/ml) and AUC (0-8) (47.5 ng X h X ml-1) in PM subjects were significantly lower than in the EM subjects (28.2 ng/ml and 94.7 ng X h X ml-1). There was a tendency to a higher incidence of side-effects in the PM group. Although the difference did not achieve statistical significance (0.1 greater than p greater than 0.05), all the PM subjects experienced sedation compared to only two in the EM group. Differences in blood pressure and pulse rate between the two groups were small. It is concluded that the oxidative metabolism of indoramin is subject to genetic polymorphism, which is probably under the control of the same gene locus as that influenci...Continue Reading


Sep 17, 1977·Lancet·A MahgoubR L Smith
Jan 1, 1979·Drug Metabolism Reviews·J R Idle, R L Smith
Jan 1, 1984·European Journal of Clinical Pharmacology·H M NorburyS J Warrington
Jan 1, 1983·European Journal of Clinical Pharmacology·H M NorburyS J Warrington
Dec 1, 1983·Clinical Pharmacology and Therapeutics·M S LennardH F Woods
Jan 1, 1983·European Journal of Clinical Pharmacology·R A FranklinD Stevenson
Jul 1, 1982·Clinical Pharmacology and Therapeutics·N S OatesR L Smith
Jan 1, 1982·Current Medical Research and Opinion·G N VolansT Frost
Mar 1, 1981·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R A FranklinT Ward
Feb 1, 1980·European Journal of Clinical Pharmacology·L BertilssonH U Schulz

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Mar 1, 1988·Biopharmaceutics & Drug Disposition·D M PierceR A Franklin
Jan 1, 1989·European Journal of Clinical Pharmacology·K Brøsen, L F Gram
Apr 1, 1997·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·M J de GrootN P Vermeulen
Dec 1, 1990·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·D M Pierce
Jan 1, 1988·European Journal of Clinical Pharmacology·D M PierceR A Franklin
Sep 5, 2002·British Journal of Clinical Pharmacology·Rashmi R Shah
Feb 6, 2004·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Rashmi R Shah
Jan 1, 1991·Fundamental & Clinical Pharmacology·G Alván
Jan 1, 1995·Drug Metabolism Reviews·M Spatzenegger, W Jaeger
Feb 1, 1993·Pharmacology & Therapeutics·A K DalyJ R Idle

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