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Eur J Clin Pharmacol. 1987;33(1):59-65.

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

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  • 1Drug Metabolism and Pharmacokinetics Section, Wyeth Research (UK) Ltd., Maidenhead, Berkshire.


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 influencing debrisoquine oxidation. The clinical consequences are discussed.

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