wide differences in xenobiotic responses due to inter-individual variation,

demographics, age, gender, ethnicity, and race. These differences are attributed to

a wide array of factors such as pharmacogenetics variations, gastrointestinal and

microbial metabolism of drugs, bioavailability, and first-step metabolism in the liver

and renal excretion. Elderly individuals are one of the most vulnerable age groups to

adverse drug reactions (ADRs) due to multiple comorbidities, co-medications, and

declining functions of the gastrointestinal-hepatic-renal systems. Age-related

debilitating conditions tend to enhance the incidence to ADRs and hospital

readmissions due to cognitive impairment, inappropriate drug use, and drug-drug,

drug-diet, and drug-herbal interactions. Collectively, all these situations make it

highly challenging for the physicians, nurses, pharmacists, and surgeons to make

drug dose adjustment decisions for the geriatric patients. Healthcare providers

should always ask their patients about herbal and dietary supplements’ use and

discourage concomitant ingestion of botanical products and fruit juices, especially

grape fruit juice, with prescription drugs. Systematic research by various scientific

groups and pharmaceutical companies has helped in the computation of drug dose

adjustments and decision-making easier for drug administration in elderly and frail

patients. Appropriate guidelines, equations, and formulas are available for calculat-

ing drug dosages for frail elderly patients based on serum creatinine or cystatin-C

clearance or some other biomarkers. It is important that elderly patients should be

enrolled in clinical trials for understanding the pharmacometabolomics and assess-

ment of safety, efficacy, and optimal dose schedules of new drugs. The focus of this

review is to address the age-related physiological, pharmacological, and toxicolog-

ical changes in elderly humans as well as age-related alterations in the absorption,

distribution, metabolism, and excretion (ADME) of drugs administered orally or by

other routes. We will also describe the characteristics of drug molecules that

influence the bioavailability, PK, PD, and potential interactions of prescription

drugs or over-the-counter medications taken simultaneously with fruit juices and

herbal remedies. In this review, we have selected examples of potential risks

associated with the psychotherapeutic class of drugs because the antidepressant,

antianxiety, and insomnia-treating medications are some of the most frequently

used categories of drugs by elderly men and women.

Keywords

Phamacometabolomics in elderly · Dose adjustment in elderly patients · Geriatric

pharmacology · Gut dysbiosis · Creatinine clearance · Clinical implications of

polypharmacy · Antidepressants

15.1

Introduction

During the past five decades, an increasing percentage of global population has

attained gerontologic status (>60 years). At the same time, advances have occurred

in drug development, medical technology and practice of medicine, and

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