Quinidine disposition in relation to antipyrine elimination and debrisoquine phenotype in alcoholic patients with and without cirrhosis.
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.kg-1.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.h-1) and quinidine/3-hydroxyquinidine ratio (9.9 +/- 2.1) were not different from controls (quinidine clearance: 13.45 +/- 1.9 l.h-1; quinidine/3-hydroxyquinidine: 10.3 +/- 2.7). A possible change in distribution patterns of quinidine in cirrhotics may explain these findings.
Debruyne
D
D
Division of Pharmacology, University Medical Centre, Caen, France.
Gram
L F
LF
Grollier
G
G
Camsonne
R
R
Agron
L
L
Dao
M T
MT
Lacotte
J
J
Bigot
M C
MC
Moulin
M
M
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000378:metabolism*; D000983:Antipyrine / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D003647:Debrisoquin / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011802:Quinidine / Q000493:pharmacokinetics*
D007546:Isoquinolines; D011802:Quinidine; D000983:Antipyrine; D003647:Debrisoquin