Distribution changes with age


Distribution changes with age


Important factors:
(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.


Geriatric issues

Campion EW,deLabry LO, Glynn RJ. The effect of age on serum albumin in healthy males: Report from the Normative Aging Study. J Gerontol. 1988;43:M18-M20.

Feely J, Coakley D.  Altered pharmacodynamics in the elderly.  Clin Geriatric Med. 1990; 6:269-283.

Greenblatt DJ, Sellers EM, Koch-Weser J. Importance of protein binding for the interpretation of serum or plama drug concentrations. J Clin Pharmacol. 1982;22:259-263.

Hammarlund ER, Ostrom JR, Kethley AJ. The effects of drug counseling and other educational strategies on drug utilization in the elderly. Med Care. 1985;23:165-170.

Hanlon JT, Schmader KE, Koronkowski Mj, et al.  Adverse drug events in high risk older patients. J Am Geriatr Soc. 1997; 45(8):945-8.

Frontera WR, Hughes VA, Lutz KJ, Evans WJ. A cross-sectional study of muscle strength and mass in 45- to 78-year-old men and women. J Appl Physiol. 1991;71:644-650.

Lamy PP. Physiological changes due to age: pharmacodynamic changes of drug action and implications of therapy.  Drugs Aging. 1991;1:385-404.

Levy RA.  Therapeutic inequivalence of pharmaceutical alternates.  Amer Pharm.  1985; April: 28-39.

MacLennan WJ, Martin P, Mason BJ. Protein intake and serum albumin levels in the elderly. Gerontology. 1977;23:360-367.

Schmucker DL. Aging and drug disposition: An update. Pharmacol Rev. 1985;37:133-148.

Thoreson J. Drug Metabolism and Drug/Drug Interactions from a Geriatrics Perspective. Clin Ger. 1997; 5: 57-74.

Tregaskis BF, Stevenson IH.  Pharmacokinetics in old age.  Br Med Bulletin. 1990; 46: 9-21.

Wilcox SM, Himmelstein, Inappropriate drug prescribing for the community-dwelling elderly. JAMA. 1994; 272:292-296  


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