Background/Objective: Numerous age-related changes in hepatic structure and function have been described, although liver function seems to be quite well maintained in old age. Few consistent and reproducible observations and a lack of correlation between structural and functional data characterize the present state of our knowledge. In contrast to renal clearance, no equally reliable method exists to estimate hepatic drug clearance. The contribution of age to altered drug clearance in the elderly is difficult to assess as drug interactions, numbers and types of drugs taken at a time, underlying disease and increased interindividual variability are superimposed to the aging process. Methods: A comprehensive computer-assisted search of the literature. Results: A decline in liver volume and blood flow and a reduction in in vitro and in vivo metabolic capacity have been shown in older subjects, and the physiologic basis of reduced hepatic drug clearance in this age group. Conclusions: After decades of research into the matter, the old and well-known aphorism ‘start lower – go slower’ is valid more than ever in the field of geriatric prescribing. Not only renally excreted drugs but also substances which are metabolized and excreted by the liver should be used at a starting dose which is 30–40% smaller than the average dose used in middle-aged adults.

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