718 blood. Oxyhaemoglobin remains red.’1

turns

brown; carboxyhaemoglobin

4400 Prince

Road, Rockville, Maryland 20853, U.S.A.

BRUCE T. ADORNATO

POLYMORPHIC HYDROXYLATION OF

DEBRISOQUINE SIR,-Dr Mahgoub and his colleagues (Sept. 17, p. 584) report that the ratio of the urinary recovery of unchanged debrisoquine (D) to that of its 4-hydroxy metabolite (4HD) was bimodally distributed in volunteers, indicating genetic polymorphism in this oxidative pathway. Our findings in 51 patients on continuous debrisoquine therapy (5-160 mg twice a day) support this conclusion. The ratio D/4HD recovery was determined in 24 h urine collections by gas chromatography.2 Our data for 30 outpatients and 21 inpatients are shown in the figure, together with those of Mahgoub et al., bringing the total frequency of to 7%. Continuous dosage "poor metabolisers" (D/4HD>21) tends to increase D/4HD ratios compared with those observed after single doses; as a result of saturation and/or inhibition of

4-hydroxylation.33 Data from

quine twice

a

’

compliant inpatients receiving 5-40 mg debrisoday further indicated that significantly more of

1.

Koch-Weser, J. in Harrison’s Principles of Internal Medicine; p. 694. New York, 1977. 2. Lennard, M. S., Silas, J. H., Smith, A. J., Tucker, G. T. J. Chromatogr. 1977, 133, 161. 3. Silas, J. H., Lennard, M. S., Tucker, G. T., Smith, A. J., Malcolm, S. L., Marten, T. R. Br.J. clin. Pharmac. (in the press).

the dose was unaccounted for as D+4HD in those with D/4HD ratios below 5 (n=16) than in those with ratios above Since debri21 (n=5) (SS±9%s.D. v. 19±12% s.D.; r