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Distribution changes with age
Distribution changes with age
(1) Decrease in lean body mass (muscle).
(2) Decrease in total body water
(3) Decrease in serum albumin (0.5-1 g/dl
(4) Increase in alpha-1 glycoprotein
(5) Increase in total body fat.
(6) Protein binding may be altered.
Decreases in total body water will lead to a much smaller volume of distribution for water soluble drugs. Conversely, increases in total body fat will result in a larger volume of distribution for lipid soluble drugs. These factors along with age-related changes in drug clearance, can have a profound impact on the eventual steady-state concentrations.
Total protein values are usually stable because of the increase in alpha-1 glycoprotein. The changes in albumin concentration with age alone are not clinically significant. However, if the patient is also malnourished (often encountered in the elderly), a clinically significant increase in free drug serum concentration may occur. For extensively protein-bound drugs such as phenytoin, whose binding is reduced due to hypoproteinemia, one should expect both therapeutic and toxic events at lower total serum concentrations. The binding affinity of albumin may also decrease with age, which may also increase free fractions of highly bound drugs.
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