Assessment of drug metabolism in hepatic disease: comparison of plasma kinetics of oral cyclobarbital and the intravenous aminopyrine breath test.

Abstract

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.

• Authors: U Breyer-Pfaff, H Seyfert, M Weber, E H Egberts
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 26 Issue 1 Pg. 95-101 ( 1984) ISSN: 0031-6970 [Print] Germany
• PMID: 6143671 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Barbiturates
• Pharmaceutical Preparations
• Aminopyrine
• Carbon Dioxide

Topics

• Adolescent
• Adult
• Aged
• Aminopyrine (administration & dosage, metabolism)
• Barbiturates (blood)
• Breath Tests
• Carbon Dioxide (metabolism)
• Fatty Liver (metabolism)
• Half-Life
• Hepatitis, Viral, Human (metabolism)
• Humans
• Injections, Intravenous
• Kinetics
• Liver Cirrhosis (metabolism)
• Liver Diseases (metabolism)
• Middle Aged
• Pharmaceutical Preparations (metabolism)