Abstract
Factors affecting biological variations in debrisoquine-oxidation polymorphism were investigated in a population of 3065 unrelated supposedly healthy Caucasian subjects, ages 35 to 50 years. This population, including 1526 men and 1539 women, was used to determine whether the debrisoquine-oxidation phenotype can be related with environmental factors such as alcohol intake, smoking habits or medication; with morphological variables; or with 22 blood constituents and some pathological states. A single dose of 10 mg of debrisoquine sulfate was administered to determine the oxidation phenotype. A metabolic ratio (debrisoquine/4-hydroxydebrisoquine) of 10.0 defined a poor metabolizer [frequency of 8.2% (SD 1.0%)] in this sample. Dose recoveries of debrisoquine excretion (mean and SD) were 8.9% (11.9%) and 45.1% (32.2%) in extensive and poor metabolizers, respectively. The mean (SD) amount of debrisoquine administered that was excreted in urine as 4-hydroxydebrisoquine was 17.4% (17.3%) in extensive metabolizers and 0.5% (0.9%) in poor metabolizers. The main factors differing significantly between poor and extensive metabolizers were mean cell volume, mean corpuscular hemoglobin concentration, albumin, and ponderal index. No other blood constituents (e.g., cholesterol, glucose) differed between poor and extensive metabolizers. The lack of correlation with most of the variables tested is of interest in clinical trials, because our findings indicate that no subgroups will be required, making selection of subjects easier.
The relationship between debrisoquine oxidation phenotype and the pharmacokinetics and pharmacodynamics of propranolol.
