Diminution of Physical Function and Its Effects on Drug Disposition

Within the medical community it has been acknowledged that elderly patients often respond to drug therapy differently from their younger counterparts. Aside from alteration of various PK and PD processes, elderly patients tend to suffer from a number of diseases and, thus, have more complex dosage regimens. Additionally, a variety of physical limitations prevalent among the elderly may hinder their ability to self-administer medication.

Elderly patients are the primary consumers of drug products today. As the geriatric population is rapidly growing in the developed countries, the impact of the elderly in the medical and pharmaceutical context will increase further. The effect of aging on drug disposition, efficacy, and safety has been rarely investigated in geriatrics. Before discussing the actual changes that occur with aging, four points must be stressed. First, because of wide variation among older individuals, it is very difficult to quantify the extent of changes that occur within this population. Second, most of these changes are related to the fact that, with increasing age, there is an overall decrease in the capacity of homeostatic mechanisms to respond to physiological changes. Moreover, with increasing age most patients suffer from numerous diseases that potentially affect the efficacy and safety of drugs administered for another illness. Physical impairments and the reduced cognitive ability may also affect the compliance of the elder patients.


During the past decade, numerous articles reviewing the effects of aging on drug delivery and PK processes according to the LADME model (i.e., liberation, absorption, distribution, metabolism, and elimination) have been published (106-123). An outline of the observations made in these reports is supplied in Table 5. The liberation and absorption are the predominant processes that will be covered in depth in this chapter as these can most easily be manipulated through formulation techniques.

Peroral administratioii/iiitestinal absorption First of all, there is a decrease in gastric secretion that causes the elevated pH that has been noted in elderly patients (106-126). This condition is commonly referred to as hypochlorhydria or, in severe cases, achlorhydria and may be the result of atrophic gastritis (115,125-127). It may result in drug degradation in the stomach and, hence, incomplete bioavailability. Drugs that are degraded in the acidic environment of the stomach (e.g., penicillin), however, may actually have an increased extent of absorption in elderly patients because less acid is available (107,108,115,125-127).

There appears to be an ongoing dispute over whether or not gastric-emptying rate (GER) and GI motility are affected by the aging process (107,108,116,125,128-134). Most studies tend to suggest that there is, indeed, a decrease in GER as the body ages. As GER is the primary physiological determinant of the rate of absorption of solid oral dosage forms, one can see that a decrease in GER may result in a subsequent decreased rate of absorption, particularly when coupled with the compromised blood flow to the GI track is also noted in elderly patients. Additionally, unpredictable GER has a significant influence on extended-release formulations, as it becomes difficult to predict whether or not acceptable blood levels will be obtained (115). To circumvent the possible problems that may arise from a decrease in GER, a liquid or readily disintegrating formulation may be used. In most instances, this decrease in the rate of absorption does not necessarily

Table 5 Changes in Pharmacokinetic Processes Observed with Aging





Gastric pH

Drug dissolution, drug stability, mucosal

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