Genetically determined oxidation capacity and the disposition of debrisoquine.

摘要: 1 The disposition in urine of debrisoquine and its hydroxylated metabolites has been studied subjects the 'extensive metabolizer' (EM; n = 5) 'poor (PM; phenotypes. 4-hydroxylation by PM following a 10 mg oral dose was capacity-limited displayed significant dose-dependency over range 1-20 mg. In contrast, EM subjects' ability to perform this metabolic oxidation did not deviate from first-order kinetics 10-40 2 plasma (n 4) 3) subjects. Whilst significantly higher levels at all time points h post-dosing, values for areas under concentration-time curve (EM: 105.6 +/- 7.0 ng ml-1 h; PM: 371.4 22.4 h, 2P less than 0.0001), neither half-life 3.0 0.5 3.3 0.4 h) nor renal clearance drug 152.8 30.3 ml min-1; 137 4.5 min-1) inter-phenotype differences. 3 results these investigations show that phenotyping individuals status means 'metabolic ratio' derived single 0-8 sample sound kinetic basis. differences between two phenotypes would strongly suggest defect manifested is one pre-systemic elimination capacity.