Trimethadione metabolism in patients with normal liver and in patients with chronic liver disease.
Serum dimethadione (DMO)/trimethadione (TMO) ratios after oral administration of TMO have been investigated in 10 patients with normal livers, 8 patients with hepatoma and 8 patients with hepatoma and cirrhosis. Serum concentration ratios of DMO to TMO at 4 h after oral administration of TMO in patients with chronic liver disease were significantly decreased by 27% for those with hepatoma and 52% for those with hepatoma and cirrhosis. Serum DMO/TMO ratios at 4 h correlated well with liver function characteristics (total protein r = 0.741, plasma albumin r = 0.826, total bilirubin r = -0.725, cholinesterase r = 0.853) as well as with pharmacokinetic parameters (total body clearance r = 0.852, half-life r = -0.636) in both patients with normal livers and patients with chronic liver disease. This study suggests that serum DMO/TMO ratios in a blood sample obtained by a single collection after an oral administration of TMO might provide a clinically useful index of the hepatic drug-oxidizing capacity in an individual patient with chronic liver disease without determining the liver function characteristics or the pharmacokinetic parameters.
Tanaka
E
E
Institute of Community Medicine, University of Tsukuba, Ibaraki-ken, Japan.
Ishikawa
A
A
Ono
A
A
Okamura
T
T
Misawa
S
S
D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002908:Chronic Disease; D004114:Dimethadione / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008111:Liver Function Tests; D008113:Liver Neoplasms; D008297:Male; D008875:Middle Aged; D010080:Oxazoles / Q000378:metabolism*; D014293:Trimethadione / Q000378:metabolism* / Q000493:pharmacokinetics
D010080:Oxazoles; D004114:Dimethadione; D014293:Trimethadione