ABSTRACT
Analysis of the drugs used at the time of hepatic injury was carried out in a group of patients consecutively admitted to medical wards during a 10 years period (1965-1975). One drug was the possible cause in 26% of the patients and 74% of them were treated with multiple drug therapy. The most common drugs associated with liver damage have been sulphonamides, oral contraceptives, nitrofurantoin, methyldopa and phenothiazine derivatives.
Subject(s)
Chemical and Drug Induced Liver Injury/etiology , Drug Therapy, Combination/adverse effects , Adult , Aged , Chemical and Drug Induced Liver Injury/epidemiology , Female , Finland , Humans , Male , Middle AgedABSTRACT
In man the liver drug metabolizing ability may be determined by assaying drug kinetics after its administration or by measuring activity of drug metabolizing enzymes from liver biopsies. Little is known about the relationship between these parameters. We investigated the problem by determining in vivo (antipyrine kinetics) and in vitro (cytochrome P-450) indices of drug metabolism in 150 consecutive patients with diagnostic liver biopsy. In patients with normal liver histology cytochrome P-450 content ranged 10.3 umole/g and the half-life 9.5 hrs. In general, alterations in liver histology were related to the changes in drug metabolism; the patients with severe changes had prolonged half-life and low cytochrome P-450, whereas the changes in those with slight parenchymal alterations were less pronounced. The relationship between in vivo and in vitro drug metabolism was non-linear in the whole material, and linear when comparing severe ill patients with controls or in subjects with closely equal liver histology. The results emphasize the importance of evaluating the liver histology when investigating in vivo and in vitro drug metabolism in man.
