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Debrisoquin hydroxylation polymorphism was studied in 326 unrelated healthy Turkish volunteers. Debrisoquin sulfate (10 mg) was administered to subjects, and debrisoquin and 4-hydroxydebrisoquin were determined in the 0- to 8-hour urine samples. Debrisoquin oxidation was polymorphic, with 11 subjects (3.37%; 95% confidence interval, 1.69% to 6.07%) phenotyped as poor metabolizers. The metabolic ratio between debrisoquin and 4-hydroxydebrisoquine in 8-hour urine samples ranged from 0.02 in extensive metabolizers to 263.8 in poor metabolizers. The proportion of poor metabolizers was found to be in the range observed in the other white populations studied. Clinical Pharmacology and Therapeutics (1994) 55, 399–401; doi:10.1038/clpt.1994.48

Plasma concentrations of unconjugated homovanillic acid (pHVA) reflect both central nervous system (CNS) and peripheral dopamine metabolism. Debrisoquin sulfate (DBQ) blocks peripheral, but not CNS, production of HVA from dopamine. Administration of DBQ has been used to decrease the proportion of peripherally produced HVA in pHVA measurements, making such measurements more reflective of CNS turnover of dopamine. We studied the relationships between DBQ dose, plasma DBQ (pDBQ) levels, and changes in pHVA in a group of 21 subjects (9 normal controls and 12 with Tourette's syndrome). DBQ dose was moderately correlated with pDBQ levels (r = 0.63, p = 0.002). Subjects (n = 8) with mean pDBQ levels above 60 ng/ml had a 48% to 66% decrease in mean pHVA levels; this may reflect nearly complete inhibition of peripheral HVA production. Subjects (n = 13) with mean pDBQ levels below 55 ng/ml had decreases in pHVA levels from 10% to 58%. No debrisoquin was detected in cerebrospinal fluid samples. These data suggest that pDBQ levels above 60 ng/ml are sufficient to assure substantial inhibition of peripheral HVA production and that monitoring pDBQ levels may be useful when employing this method for studying CNS metabolism.

Central dopaminergic (DA) function in children was assessed by monitoring plasma-free homovanillic acid (pHVA) levels after brief (18 hour) administration with debrisoquin sulfate, a peripherally active antihypertensive agent that blocks peripheral, but not central, HVA production. Brief debrisoquin administration resulted in marked reductions in pHVA in each of six patients studied. In five of the six patients, post-debrisoquin pHVA levels remained relatively stable over the six-hour period of observation. No significant cardiovascular or behavioral side effects of debrisoquin were observed. The brief debrisoquin administration method appears to be a safe, simple, and potentially valid peripheral technique for evaluating aspects of central dopaminergic function in children with neuropsychiatric disorders. Additional work is needed to further establish this method's validity and reliability.

Sixty-three hypertensive patients were treated with debrisoquin sulfate, a new sympathetic blocking drug, for periods of 6 to 33 months. Good initial blood pressure control was achieved in over 80% of this series, and over 75% maintained good or fair control over the period of the study. At least one-half of the patients required increases in dosage or the addition of a diuretic with the passage of time. Side effects, especially postural dizziness, were not uncommon but seldom necessitated withdrawing the drug. Debrisoquin is an effective and potent antihypertensive agent, and the development of tolerance and side effects have not so far given rise to practical difficulties in blood pressure control.