However, absorption problem seems to occur in the elderly subjects due to the

co-existing disease conditions like atrophic gastritis, bile reflux disorder, gut motility

problems, constipation, dysbiosis, and insufficient circulation in the gastrointestinal

tract. Aging-associated drug absorption changes can lead to day-to-day variations in

the bioavailability, first pass effect, and therapeutic blood concentrations among the

geriatric patients (Italiano and Perucca 2013). The total body fluid (TBF) and cell

mass (CM) decrease are parallel in the aging person. Although the extracellular fluid

(ECF) constitutes a large proportion of TBF in elderly, the loss of TBF significantly

impacts on the intracellular fluid (ICF). Thus, the disproportional shifts between ICF

and ECF are mainly responsible for age-related alterations in unchanged drug and/or

its metabolite distribution in the body and PK values (Mangoni and Jackson 2003).

Malnutrition, thyroid deficiency, kidney disease and hemodialysis, and metabolic

disorders are frequent among elderly patients, which adversely affect not only the

water balance and electrolyte homeostasis but also the quality of life (Shehab-Eldin

et al. 2020).

Generally, the elderly population has increased susceptibility to the iatrogenic or

toxic effects of drug, because of their diminished physiologic reserve capacity of

drug-metabolizing and excretory organs. The baseline functions of the gastrointesti-

nal tract, microbiota, liver, and kidneys decline with ageing. In addition, there is a

higher incidence of concomitant disorders that require multiple drug therapy by

elderly patients, resulting in increased possibility of ADRs due to polypharmacy.

Self-medication with micronutrients, herbal remedies, and dietary supplements is

also common among the elderly patients, and the combinations can elicit clinically

important adverse drug-herb-diet interactions. To date, there is a lack of consistent

criteria and evaluation of potential underlying pathophysiological conditions that are

responsible for causing the large differences in the metabolic disposition and PK/PD

parameters between young adult and elderly subjects (Streeter and Faria 2017).

Hence, assessment of pharmacometabolomics is important for drug dose adjustment

in the elderly population because every individual process associated with absorp-

tion, distribution, metabolism, and disposition (ADME) of drugs administered orally

or by other routes gets altered in old age (Hilmer 2008). It is also important that

elderly patients should be enrolled in clinical trials for learning more about the

pharmacometabolomics and assessment of long-term safety, efficacy, and dosing

schedules of new drugs. The International Association of Gerontology and Geriatrics

in conjunction with WHO has suggested that the new drugs intended to be used in

the older population should undergo well-controlled, randomized, double-blind

clinical trials in nursing home residents. Such clinical trials are desperately needed

to determine the benefits and harms of medications administered in older persons

(Tolson et al. 2011). Prescribing guidelines have been developed, and several

investigators have recommended reducing inappropriate polypharmacy to minimize

the iatrogenic risks of drugs in frail elderly and cancer patients (Scott et al. 2015;

Sharma et al. 2016; Tjia and Lapane 2017). This review provides evidence regarding

the potential prevalence of polypharmacy and suggests ways to reduce drug-induced

harm due to inappropriate medication use in the geriatric patients.

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