No abstract

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 less than 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 less than 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.

SummaryOf 125 patients aged 65 years or over, with atrial fibrillation taking warfarin for at least 12 months, with a standard deviation (SD) of prothrombin time, expressed as the International Normalized Ratio (INR) >0AE5 over the previous 6 months, 40 were randomized to continue with usual clinic care and 85 to receive education about warfarin. Of these, 44 were randomized to self-monitor their INR and 41 returned to clinic. Compared with the previous 6 months there was a significant increase in percentage time within the therapeutic range for the 6 months following education [61AE1 vs. 70AE4; mean difference 8AE8; 95% confidence interval (CI): )0AE2-17AE8; P ¼ 0AE054] and following education and self-monitoring (57 vs. 71AE1; mean difference 14AE1; 95% CI: 6AE7-21AE5; P < 0AE001), compared with those patients following usual clinic care (60AE0 vs. 63AE2; mean difference 3AE2; 95% CI: )7AE3-13AE7). Using the same comparative periods, the INR SD fell by 0AE24 (P < 0AE0001) in the group allocated to education and self-monitoring, 0AE26 (P < 0AE0001) in the group receiving education alone and 0AE16 (P ¼ 0AE003) in the control group. Intergroup differences were not statistically significant (intervention groups 0AE26 ± 0AE30 vs. control 0AE16 ± 0AE3, P ¼ 0AE10). Quality-of-life measurements and health beliefs about warfarin were unchanged (apart from emotional role limitation) with education or education and self-monitoring. Patient education regarding anticoagulation therapy could be a cost-effective initiative and is worthy of further study.

No abstract

Aging in humans is associated with marked declines in the disposition of numerous drugs and other xenobiotics that require hepatic biotransformation before elimination. Considerable pharmacokinetic evidence in humans, coupled with data on in vitro liver microsomal monooxygenase functions generated in inbred male rodent models, has implicated impaired liver phase I drug metabolism (i.e., diminished efficacy of microsomal monooxygenases) in reduced drug clearance in the elderly. This study (1) assessed the in vitro activities and amounts of liver microsomal monooxygenases as a function of donor age and gender in healthy humans and (2) provides the most extensive and comprehensive data to date demonstrating the absence of significant age- and gender-dependent differences in the activities and contents of human liver monooxygenases.