Pharmacokinetic Assessment of the Effect of Age on the Disposition and Pharmacologic Activity of Drugs
Aging is associated with a number of physiologic changes. These include decreases in plasma albumin concentration, lean body mass and total body water, cardiac output, renal function (glomerular filtration and renal tubular secretion), and activity of drug metabolizing enzyme systems (reviewed in refs. 1–3). Superimposed upon these age-related changes, and difficult if not impossible to distinguish from these in a clinical setting, are the cumulative effects of environment (including smoking, medications, and diet) and disease. It is not surprising, therefore, that there is evidence suggesting age-dependent changes in the absorption, distribution, metabolism, and excretion of drugs. Such changes may be expected to result in corresponding modifications in the intensity and duration of pharmacologic effects but age may also affect the intrinsic response of receptor sites to drugs. Since the pertinent literature on pharmacokinetics related to advanced age has been reviewed thoroughly in several recent publications (1–3), the purpose of this presentation will be to focus on the pharmacokinetic principles that must be considered in the design, analysis, and interpretation of studies of the effect of age on the disposition and pharmacologic activity of drugs.
KeywordsTotal Body Water Total Clearance Renal Tubular Secretion Pharmacokinetic Consideration Hepatic Drug Clearance
Unable to display preview. Download preview PDF.
- 1.Gorrod, J. W. 1974. Absorption, metabolism and excretion of drugs in geriatric subjects. Geront. Clin. 16: 30–42.Google Scholar
- 2.Triggs, E. J., and Nation, R. L. 1975. Pharmacokinetics in the aged: a review. J. Pharmacokin. Biopharm. 3: 387–418.Google Scholar
- 3.Crooks, J., O’Malley, K., and Stevenson, I. H. 1976. Pharmacokinetics in the elderly. Clin. Pharmacokin. 1: 280–296.Google Scholar
- 4.Klotz, U., Avant, G. R., Hoyumpa, A., Schenker, S., and Wilkinson, G. R. 1975. The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J. Clin. Invest. 55: 347–359.Google Scholar
- 5.Wallace, S., Whiting, B., and Runcie, J. 1976. Factors af- fecting drug plasma of elderly patients. Brit. J. Clin. Pharmacol. 3: 327–330.Google Scholar
- 6.Levy, G. 1976. Clinical implications of interindividual differences in plasma protein binding of drugs and endogenous substances. In: The Effect of Disease States on Drug Pharmacokinetics. Am. Pharm. Assoc. Acad. Pharm. Sci., Washington, chapter 9.Google Scholar
- 7.Wilkinson, G. R., and Shand, D. G. 1975. A physiologic approach to hepatic drug clearance. Clin. Pharmacol. Ther. 18: 377–390.Google Scholar
- 8.Levy, G. 1973. Correlation between drug concentration and drug response in man - pharmacokinetic considerations. Proc. 5th Int. Congr. Pharmacol. 3: 34–55.Google Scholar