| Abstract: | 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. |
