Learning Objective
By the end of this section, students should be able to describe how aging affects drug absorption, distribution, metabolism, and excretion (ADME), and understand why older adults often require dose adjustments to avoid drug toxicity.
Age-Related Changes in Pharmacokinetics
Aging alters the way drugs move through the body, often leading to higher plasma concentrations and increased risk of toxicity if standard doses are used.
1. Absorption
- Mostly unchanged with age.
- Oral bioavailability of most drugs remains stable.
2. Distribution
- ↓ Total body water → ↓ volume of distribution (Vd) for hydrophilic drugs → ↑ plasma concentration.
- ↑ Body fat → ↑ Vd for lipophilic drugs → ↑ half-life.
- ↓ Serum albumin (sometimes) → affects highly protein-bound drugs (e.g., warfarin, phenytoin) → ↑ free drug concentration.
3. Metabolism
- ↓ Hepatic mass & blood flow → ↓ first-pass metabolism, ↓ hepatic clearance.
- Phase I metabolism (oxidation, reduction, hydrolysis) decreases → drugs relying on Phase I are more affected (e.g., benzodiazepines, theophylline).
- Phase II metabolism (conjugation, glucuronidation) is relatively preserved → drugs like lorazepam, oxazepam, temazepam are safer in the elderly.
4. Excretion
- ↓ Renal mass & blood flow → ↓ GFR → ↓ renal clearance.
- Drugs primarily excreted by the kidneys (e.g., aminoglycosides, digoxin, lithium, vancomycin) require dose adjustments.
USMLE Step 1 Pearls
- Hydrophilic drugs → ↑ plasma concentration → risk of toxicity
- Lipophilic drugs → ↑ half-life → prolonged effects
- Phase I metabolism ↓, Phase II preserved → choose Phase II drugs in the elderly
- Renally cleared drugs → monitor kidney function; adjust doses
- Always consider “start low, go slow” in geriatric pharmacotherapy
