Dr. Witassek is the recipient of a stipend of the Paul-Martini-Stiftung
Abnormal Glucuronidation of Zomepirac in Patients with Cirrhosis of the Liver
Article first published online: 21 SEP 2007
Copyright © 1983 American Association for the Study of Liver Diseases
Volume 3, Issue 3, pages 415–422, 1983
How to Cite
Witassek, F., Bircher, J., Huguenin, P. and Preisig, R. (1983), Abnormal Glucuronidation of Zomepirac in Patients with Cirrhosis of the Liver. Hepatology, 3: 415–422. doi: 10.1002/hep.1840030322
- Issue published online: 21 SEP 2007
- Article first published online: 21 SEP 2007
- Manuscript Accepted: 15 DEC 1982
- Manuscript Received: 24 AUG 1982
- Swiss National Science Foundation, Hochschulstiftung Berne, and Cilag-Chemie AG.
The disposition of zomepirac was investigated in 18 patients with various liver diseases and in 10 healthy normal subjects in order to further test the hypothesis that glucuronidation of drugs may be spared in liver disease. Severity of the liver disease was assessed by the galactose elimination capacity. Following oral administration of zomepirac (200 mg), plasma and urinary drug concentrations were measured by high-pressure liquid chromatography. Urine was assayed before and after alkaline hydrolysis. The apparent oral clearance of zomepirac was 3.7 ± S.D. 1.2, 3.0 ± 0.8, and 1.8 ± 0.6 mlmin_1kg_1 in normal subjects, patients with mild liver disease, and cases with cirrhosis, respectively. In patients with liver disease, the reduction in zomepirac clearance was significantly correlated with the abnormalities in galactose elimination capacity (r = 0.83, n = 18), suggesting that the functioning liver cell mass was the major determinant of the rate of zomepirac disposition. These results are not consistent with the original hypothesis but suggest that–in contrast to ether-glucuronidation–ester-glucuronidation may be abnormal in liver disease. Dosage adjustments may, therefore, be necessary in patients with cirrhosis of the liver.