Abstract |
The article examines the pharmacokinetic behavior of environmental chemicals and drugs that are altered during aging. Absorption may be the least sensitive parameter to age-related perturbations. However, pulmonary and dermal absorption, which are both dependent upon passive diffusion, do appear to decline. In contrast, no evidence supports a decrease in passive transport across the gut wall, while active processes in the GI tract do decline in the aged. Distribution is affected by changes in body composition, the decrease in lean body mass resulting in a decreased Vd for water-soluble chemicals and enhanced persistence of lipophilic ones. Changes in protein binding and blood flow also alter the concentration of unbound chemicals reaching the target site. The changes in metabolism are extremely complex, with increases, decreases, and no change being observed for different enzymes with varying substrates in different tissues, sexes, strain, and species. Only excretion tends to consistently change with age, in large part due to the altered blood flow, structure, and physiology of the kidney. Hepatic and pulmonary elimination also tend to decline with age. |