like β-N-methylamino-alanine, which contributes to β-amyloid accumulation in

Alzheimer’s disease (Bhattacharjee and Lukiw 2013). Over-production of trypto-

phan metabolites by the gut microbiota may increase oxidative stress resulting in cell

death, tau phosphorylation, and tangle formation in Alzheimer’s disease (Westfall

et al. 2017). Therefore, probiotics and dietary amino acid balance, especially trypto-

phan, remains an important strategy to promote healthy gut microbiome environ-

ment and to prevent neurological disorders and other NCDs.

15.4

Age-Related Alterations in Drug Absorption, Distribution,

Metabolism, and Excretion (ADME) and Consequences

Age-associated pathophysiological changes in the body organs not only alter

ADME, but also pharmacokinetic (PK) and pharmacodynamics (PD) parameters.

In simple terms, PK is defined as what the body does to the drug in order to make the

drug metabolites water-soluble for excretion into the bile, feces, and urine, while PD

is defined as what the drug and/or its metabolites do to the body to produce

pharmacological actions. The major components of PK consist of volume of distri-

bution (Vd), maximal concentration (Cmax) reached after absorption, time to reach

maximal concentration (Tmax), half-life (T1/2), area under the curve (AUC), and

bioavailability. Most of the PK components get altered with age in every man and

woman. Some other factors involved in causing differences in PK and PD are inter-

individual variability (slow and fast metabolizers), inter-ethnic and inter-racial

variations, and exposure to herbal and dietary supplements.

15.5

Absorption and Bioavailability

Aging is associated with alterations in gastrointestinal motility, gut hormones, and

digestive secretions, blood flow, and absorptive surface of the GI tract. Generally, in

elderly individuals, absorption problems are more likely to be related to any under-

lying disease conditions, e.g., diminished splanchnic blood flow (due to cardiac

insufficiency) or atrophic gastritis (Murad and Kitzman 2012; Birnbaum et al. 2003).

Gastrointestinal pH can markedly affect oral drug absorption and bioavailability

because of the significant influence on drug dissolution, solubility, release, stability,

and intestinal permeability. Atrophic gastritis affects the absorption from the stom-

ach and bioavailability of micronutrients like dietary vitamin B12, iron, and calcium

may be perturbed (Rodriguez-Castro et al. 2018). Ideally the digestion of dietary

vitamin B12 takes place in the presence of gastric acid in the stomach and the

binding of vitamin B12 to the intrinsic factor happens further in the small intestine.

This malabsorption could be corrected by the administration of diluted HCl and with

the protein-bound vitamin B12. Another alternative to enhance the vitamin B12

absorption in individuals with atrophic gastritis is by lowering bacteria in the

proximal small intestine by antibiotics. However, oral vitamin B12 supplements or

foods fortified with vitamin B12 can be prescribed or recommended in elderly

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

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