Assessment of drug metabolism in hepatic disease: comparison of plasma kinetics of oral cyclobarbital and the intravenous aminopyrine breath test.
The exhalation of 14CO2 derived from an i.v. tracer dose of [dimethylamine-14-C]aminopyrine has been investigated in normal controls and patients. They subsequently ingested 200 mg cyclobarbital calcium in the evening and the decline in the plasma drug level over the following 2 days was measured by thin-layer chromatography. The peak specific activity of exhaled 14CO2 occurred 0.5-2 h after 14C-aminopyrine injection in the absence of liver disease and in non-cirrhotic liver disorders. It was delayed in certain patients with cirrhosis. Compared to 8 medically healthy subjects, 10 patients with acute viral hepatitis, 8 with cirrhosis and 10 with fatty liver exhibited a significantly increased half-life of 14CO2 exhalation. Normal mean values were found in 12 patients with non-cirrhotic alcoholic liver disease and in 14 patients with non-hepatic diseases. The cyclobarbital (CB) half-life was prolonged and the clearance reduced in patients with viral hepatitis, cirrhosis or alcoholic liver damage as compared to data from 17 control subjects. Due to a larger apparent volume of distribution, patients with fatty liver disease had an increased CB half-life, although its clearance was normal. A close negative correlation was detected between the clearance and the logarithm of the CB level measured 36 h after drug ingestion. The oral CB test evaluated from a single blood sample taken about 36 h after drug administration appears to be a useful indicator of human drug metabolising capacity. Discrimination between patients with and without disordered liver function was similar in the two drug elimination tests.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000632:Aminopyrine / Q000008:administration & dosage / Q000378:metabolism*; D001463:Barbiturates / Q000097:blood*; D001944:Breath Tests; D002245:Carbon Dioxide / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism; D006207:Half-Life; D006525:Hepatitis, Viral, Human / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008103:Liver Cirrhosis / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D001463:Barbiturates; D004364:Pharmaceutical Preparations; D000632:Aminopyrine; D002245:Carbon Dioxide