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Proceedings: A correlation between the response to debrisoquine and the amount of unchanged drug excreted in the urine.

The correlation between responsiveness to the adrenergic blocking agent debrisoquine and the amount of unchanged drug excreted in the urine has been investigated in normotensive subjects and in a number of hypertensive outpatients as part of a study on the therapeutic implications of metabolism of this hypotensive agent. Preliminary experiments showed that single oral doses (40 mg) of [14CI-debrisoquine were well absorbed (75% of 14C was excreted in the urine in 24 h) and that the drug was metabolized by hydroxylation to an extent which appeared to vary between subjects (Angelo, Dring, Lancaster & Smith, unpublished data). To investigate a possible relationship between responsiveness and extent of metabolism in a larger group of subjects a g.l.c. method for the estimation of unchanged debrisoquine in urine was developed. This was a modification of the method of Hengstmann, Falkner, Watson & Oates (1974) and depends upon the hydrolytic conversion of debrisoquine to tetrahydroisoquinoline which is measured as its trichloroacetyl derivative on g.l.c. with electron capture detection using phenformin as internal standard. For the purpose of this study the blood pressure of 10 normotensive subjects with normal renal function who had received 40 mg of debrisoquine orally was recorded lying down, standing and after walking 50 yards, using a random zero sphygmomanometer, at intervals for up to 48 hours. Urine samples were collected at similar intervals for measurement of their debrisoquine content. The blood pressure of the subjects was measured on a control day at the same times but in the absence of the drug. There