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  • Title: Debrisoquine oxidation in a Finnish population: the effect of oral contraceptives on the metabolic ratio.
    Author: Kallio J, Lindberg R, Huupponen R, Iisalo E.
    Journal: Br J Clin Pharmacol; 1988 Dec; 26(6):791-5. PubMed ID: 3242585.
    Abstract:
    1. The debrisoquine hydroxylation phenotype was assessed in 211 healthy subjects of Finnish Caucasian origin. 2. A bimodal distribution was observed in the urinary debrisoquine/4-hydroxydebrisoquin ratio. Eleven subjects (about 5%) were poor metabolizers of debrisoquine, when a ratio of 12.6 was used as the cut-off point. 3. The mean metabolic ratio of 35 extensive metabolizers taking oral contraceptives was slightly lower than that of extensive metabolizers not taking contraceptives. This indicates that oral contraceptives may change the phenotyping near the metabolic ratio of 12.6. 4. The metabolic ratios were determined in eight subjects using both 4 h and 6 h urine collection times. The metabolic ratios corresponded well with each other indicating the usefulness of the shorter 4 h collection time. A study was conducted in Finland at the University of Turku on 211 participants: 130 of which were women and 81 which were men. The purpose of the study was to investigate debrisoquine hydroxylation polymorphism in the Finnish Caucasian population. Methods employed were the selection of patients who were in fairly good health and did not take any drugs except low-dose contraceptives (35 subjects). The volunteers fasted overnight and were given a 10mg tablet of debrisoquine (Declinax) with water. Urine samples were taken 6 hours after the ingestion of the tablet. Debrisoquine (D) and 4-hydrodebrisoquine (4-OH-D) concentrations were measured using the gas chromatographic method with a slight modification. The metabolic ratio (MR) to be used as an index of the debrisoquine hydroxylation capacity was determined as MR = amount excreted as debrisoquine/amount excreted as 4-hydroxydebrisoquine. Subjects with a MR 12.6 were classified as poor metabolizers. The results of the study are as follows: 11 (6 women and 5 men) poor metabolizers were discovered; 2 of the 35 women taking low-dose oral contraceptives were discovered to be poor metabolizers; the MR of the 211 volunteers was found to be similar among the sexes despite age or/and urine volume; however, the mean MR was lower in extensive metabolizers (EM) with contraceptives than in female EMs without them.
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