Departments of Medicirzc ((A ricrtric 5 ) Clinic a1 Pharnincoloq~ trtid Hadlolog. Clniuer\itj of Neiccastle Upon Tyne,
Neulcmtle lfpon T\ nc I 'nif<>d Kingdom
The aim of this study was to determine the effect of aging upon liver volume and apparent liver blood flow in healthy man. Sixty-five subjects between 24 and 91 years of age were recruited. Liver volume was quantitated by a gray scale B ultrasound scan method. Apparent liver blood flow was determined from the plasma clearance of indocyanine green, based on an assumption of no change in hepatic extraction of the dye with age.
A significant negative correlation was observed between age and both liver volume and apparent liver blood flow (p < 0.001), whether expressed in absolute terms or per unit body weight. Similarly, a significant negative correlation was observed between apparent liver blood flow per unit volume of liver (liver perfusion) and age (p < 0.005).
The reduction in liver volume, apparent liver blood flow and perfusion may at least partly account for the decline in the clearance of many drugs undergoing liver metabolism which has been noted to occur with aging in man.
The systemic elimination of a number of drugs metabolized by hepatic microsomal monooxygenase enzymes (MMOs) has been shown to decline with age in man (1.
2). The age-related fall of the specific activities of t.hese enzymes in rats, first reported hy Kato et al. ( 3 ) and subsequently confirmed by m a n y o t h e r workers. has led t.o the assumption that similar c.hanges occur in aged humans and may thus account for decreased drug elimination. We have recently measured the in i'itro specific activities of a number of' hepat.ic MMOs in histologically normal human liver specimens. many obtained from subjects with normal liver function tests undergoing routine cholecystectomy, and have found no age-related decline (4). Furthermore, in nonhuman primates, liver microsomal NADPH cytochrorne (' (P-45Oj reductase ( 5 ) and benzo[cu]pyrene hydroxylase activities are unchanged with aging (6). These findings have therefore brought into question the above assumption. We have t.herefore hypothesized t,hat changes in liver mass and