Quinidine disposition in relation to antipyrine elimination and debrisoquine phenotype in alcoholic patients with and without cirrhosis
Debruyne, D.; Gram, L.F.; Grollier, G.; Camsonne, R.; Agron, L.; Dao, M.T.; Lacotte, J.; Bigot, M.C.; Moulin, M.
International Journal of Clinical Pharmacology Research 9(5): 319-325
1989
ISSN/ISBN: 0251-1649 PMID: 2625371 Document Number: 342069
Single dose disposition of oral quinidine (400 mg sulfate) was studied in a control group of subjects (No. = 6) and in hospitalized alcoholic patients involving one group with (No. = 6) and one group without (No. = 11) hepatic cirrhosis. All subjects also underwent an antipyrine and a debrisoquine test. Patients with cirrhosis had a prolonged elimination half-life (29.5 .+-. 5.9 h) and low clearance (24 .+-. 7 ml .cntdot. kg-1 .cntdot. h-1) of antipyrine and also a considerably higher debrisoquine metabolic ratio (18.8 .+-. 3.3) than the controls, whereas the alcoholics without cirrhosis had metabolic patterns for these two test compounds comparable to those seen in the controls (antipyrine half-life: 8.8 .+-. 1.1 h and 9.8 .+-. 2.0 h; debrisoquine metabolic ratio: 3.6 .+-. 0.7 and 3.8 .+-. 1.2 for alcoholics and controls respectively). In patients with cirrhosis the apparent elimination half-life of quinidine was longer (12.8 .+-. 1.8 h) whereas after oral administration clearance of quinidine (15.6 .+-. 3.5 l .cntdot. h-1) and quinidine/3-hydroxyquinidine ratio (9.9 .+-. 2.1) were not different from controls (quinidine clearance: 13.45 .+-. 1.9 l .cntdot. h-1; quinidine/3-hydroxyquinidine: 10.3 .+-. 2.7). A possible change in distribution patterns of quinidine in cirrhotics may explain these findings.