advancement in surgical procedures, which have added to the longevity and good

quality of life. According to the WHO estimates, by the year 2050, the worldwide

elderly population (>60 years) is expected to reach 1.4 billion, which means that

1 out of 10 people will be more than 60 years of age. In some countries, this tendency

is more accelerated, e.g., in 2012, the number of people in India aged 60 years and

over was 98.5 million which has increased by 54.8% in the last 15 years (World

Alzheimer’s Report 2018).

Prevalence of multiple drug usage or polypharmacy steadily increases with age

due to the enhanced risk of non-communicable diseases (NCDs) such as neurode-

generative disorders, dementia and cognition impairment, anxiety and depression,

cardiovascular diseases, diabetes mellitus, obesity, osteoarthritis, and cancer, to

name a few. The incidence of infections, autoimmune disorders, insomnia, and

psychiatric problems also increase in the aging population (Moxey et al. 2003).

Aging is associated with liver and kidney atrophy and alterations in gastrointestinal

motility, accompanied by reduced gut secretions and blood flow, as well as reduction

in absorptive surface area of the gastrointestinal tract. The age-related pathophysio-

logical changes can alter the absorption, distribution, metabolism, and excretion

(ADME) of drugs, consequently affecting the PK and PD parameters. As opposed to

the relatively younger age groups, the geriatric subjects are more susceptible to drug-

mediated adverse reactions due to the reduced activity in cytochrome P450

coenzymes and glucuronidation/sulfation mechanisms.

Potentially inappropriate medication (PIM) is common among the elderly

(Lenander et al. 2018), and some drug-related adverse effects in the elderly are

due to the inappropriate use or overuse of drugs. There are neurological conditions

when the risk of PIM is increased, e.g., the prevalence of PIM is high among the

older adults with cognitive impairment and/or dementia ranging from 15% to 47%

population (Patel et al. 2017). This means non-adherence to doctors’ and

pharmacists’ recommendations as well as due to the use of over-the-counter

(OTC) drugs and self-medication with herbal remedies or dietary supplements can

alter the metabolism and PK/PD of prescribed drugs. Generally, doctors prescribe

pharmaceuticals according to the instructions listed in the Drug Product

Monographs, which contain the most important patient information about the needed

changes in dosage if the drug is indicated for elderly patients. Nevertheless, iatro-

genic effects of drugs are quite common among the elderly and frail patients when

the doctors, surgeons, and pharmacists are unable to correctly assess the pathophysi-

ological conditions and consult patients prior to ordering the appropriate medications

(Hedna et al. 2015).

It is well known that marked differences exist in the metabolic disposition and PK

of drugs among the infants/toddlers, young adults (<40 years), inter-individual

variation, gender, ethnicity, and elderly men and women. In comparison with the

younger counterparts, the activity of hepatic drug-metabolizing enzymes, especially

cytochrome

P450

coenzymes

and

phase

II

biotransformation,

especially

glucuronidation, is far lower in the pediatric and elderly populations. Hence, drug

dose adjustment is an essential requirement in these special groups. Most orally

administered drugs appear to be adequately absorbed in the elderly subjects.

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The Importance of Drug Dose Adjustment in Elderly Patients with Special. . .

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