Liver size in evaluating drug metabolizing capacity in man.

Abstract

Liver size, cytochrome P-450 (P-450) concentration in liver biopsy specimens and antipyrine kinetics were studied in 112 consecutive patients undergoing diagnostic liver biopsy. Compared to subjects with normal parenchyma, those with slight or severe parenchymal alterations had enlarged livers with low P-450 concentration and slow antipyrine elimination. In the normal group, the mean P-450 concentration (+/- 1 SD) was 11.10 +/- 2.14 nmol/g liver tissue and the total amount (estimated liver weight g X P-450 concentration nmol/g) 16.06 +/- 3.29 mumol. Previous therapy with enzyme inducing drugs was associated with enlarged liver in subjects with normal histological findings and with fast antipyrine elimination and high P-450 in all groups. Antipyrine elimination rate correlated with liver weight only in subjects with normal parenchyma. The total amount of P-450 was generally more closely related to its concentration than to the estimated liver weight, although in many individual cases a large liver was able to compensate a low P-450 concentration so that the total P-450 was at the normal level. Despite normal or high total P-450, in vivo drug metabolism was impaired in subjects with altered parenchyma, suggesting that other factors were limiting antipyrine elimination in liver disease.