Abstract

Dimethadione (DMO)/trimethadione (TMO) ratios in serum after oral administration of TMO were investigated in 15 normal subjects and in 20 patients with cirrhosis and esophageal varices. Severe impairment of liver function was associated with a decrease in total cholesterol, total protein and plasma albumin, or an increase in total bilirubin, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, serum gamma-glutamyl transpeptidase and indocyanine green retention rate (ICG R15). Serum concentration ratios of DMO to TMO at 2 or 4 h after oral administration of TMO in patients were significantly decreased by 67 or 66%, respectively, compared to normal subjects. DMO/TMO ratios at 2 or 4 h following oral administration of TMO were well correlated with the liver function parameters (plasma albumin r = 0.758 at 2 h, r = 0.776 at 4 h; total protein r = 0.613 at 2 h, r = 0.619 at 4 h; ICG R15 r = -0.683 at 2 h, r = -0.746 at 4 h, in patients only; cholinesterase r = 0.873 at 2 h, r = 0.908 at 4 h) as well as with pharmacokinetic parameters (total body clearance r = 0.794 at 2 h, r = 0.786 at 4 h) in both the normal subjects and the patients. It suggests that the DMO/TMO ratio obtained in a single blood sample collected after oral administration of TMO might provide a useful measure for function hepatic reserve.

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