Understanding Pharmacokinetic Changes is Imperative

Rhonda Witte, BSc

It is one thing to know how the body changes with age, but it is another to understand the effects of these changes on the body. Decreased kidney size? A smaller liver? They may sound like minor changes, but it is crucial to understand the significance of such age-related changes in terms of selecting appropriate drug therapy. Geriatric clinical pharmacology is not a large part of the general practice of medicine but with an increasing elderly population, greater knowledge in this area is required.¹ What must be kept in mind is that it is not just about what drugs should be prescribed to the elderly--it is about the right drugs that should be prescribed to a geriatric patient on an individual basis.

Pharmacokinetics

Fundamental to geriatric medicine is the understanding of age-related changes in pharmacokinetics. Such changes have profound impacts upon drug usage in the elderly population. When ignored, severe complications and even death can result from pharmacotherapy. What makes the situation even more complicated is that pharmacokinetic changes vary with the individual. Therefore, each patient must be treated with a highly individualized approach² and one patient's situation cannot set the standard for other patients to follow.

Pharmacokinetics refers to time-dependent changes of drug concentration and their metabolites in the body, or more simply, what the body does to a drug.^3,4 Specifically, pharmacokinetics includes the processes of drug absorption, distribution, metabolism and elimination.

---

Age-associated Factors Affecting Drug Pharmacokinetics in the Older Person⁵

aAbsorption (unchanged) Gastric pH Increased Intestinal mobility Decreased Intestinal emptying Decreased GI* mucosal surface area Decreased Splanchnic circulation Decreased Secretory Capacity Decreased GI* Blood Flow Diminished	bDistribution Alpha-1 Glycoprotein Increased Total Body Fat Increased Lean Body Muscle Mass Decreased Protein Affinity Diminished Plasma Albumin Diminished
cMetabolism Size of Liver Decreased Hepatic Blood Flow Decreased Phase I reactions Decreased Phase II reactions Unchanged	dElimination Filtration Fraction Increased Kidney Size Decreased Glomerular Filtration Rate Decreased Renal Plasma Flow Decreased
*gastrointestinal

---

Drug Absorption

Absorption is the process by which a drug is transported via passive diffusion across the epithelium into the portal-systemic circulation.⁴ Age-related changes in absorption are a reflection of changes to the GI tract. Such changes include decreased acid output, resulting in increased gastric pH, which may affect the ionization and solubility of particular drugs.⁵ Other changes include decreased intestinal mobility and emptying, decreased GI mucosal surface area, decreased splanchnic circulation