Pharmacokinetics Across the Lifespan
Age-related changes in pharmacokinetics (PK)—the study of how a drug is absorbed, distributed, metabolized, and excreted by the body—are a primary reason for adjusting medication administration. These physiological differences are most pronounced at the two extremes of the lifespan: infancy and old age.
Pediatric Pharmacokinetics
Infants and children are not simply 'small adults.' Their developing organ systems and unique body compositions mean that drugs are processed differently and require careful, weight-based calculations.
- Absorption: An infant's gastric pH is higher and gastrointestinal motility is slower, which can alter the absorption of some oral medications. Thinner skin and a larger surface-area-to-volume ratio also increase the risk of toxicity from transdermal absorption.
- Distribution: Due to a higher percentage of total body water and lower body fat, water-soluble drugs have a larger volume of distribution in infants, which can reduce their concentration in the body. Conversely, lower levels of circulating plasma proteins can increase the amount of unbound (active) drug for highly protein-bound medications.
- Metabolism: Key liver enzymes, such as the cytochrome P450 system, are not fully mature at birth, leading to slower drug metabolism in neonates. This activity increases rapidly during the first year of life, and in some cases, children metabolize drugs faster than adults on a weight-adjusted basis.
- Excretion: An infant's renal function, including glomerular filtration rate (GFR) and tubular secretion, is decreased at birth and matures over several months. This can prolong the half-life of medications and increase the risk of toxicity from drug accumulation.
Geriatric Pharmacokinetics
As people age, a gradual decline in organ function and changes in body composition significantly impact how medications are processed, increasing the risk of adverse drug reactions (ADRs).
- Absorption: Age-related changes in drug absorption are generally less clinically significant than other PK changes. However, decreased gastric acid and motility can affect certain drugs, and reduced blood flow can impact the absorption of some injected or transdermal medications.
- Distribution: Older adults typically have more body fat and less total body water and lean muscle mass. This leads to a larger volume of distribution and a longer half-life for fat-soluble drugs (e.g., benzodiazepines), and a smaller volume of distribution with higher initial plasma concentrations for water-soluble drugs (e.g., digoxin).
- Metabolism: Reduced liver mass, blood flow, and phase I metabolic enzyme activity can decrease the clearance of many drugs metabolized by the liver. A diminished first-pass metabolism for some oral medications can also lead to higher circulating drug levels.
- Excretion: The most significant age-related PK change is decreased renal clearance. GFR declines with age, meaning renally excreted drugs, especially those with a narrow therapeutic index (like digoxin), are at increased risk of accumulating to toxic levels.
Pharmacodynamic Changes in Older Adults
Pharmacodynamics (PD) describes the effects of a drug on the body. With age, the body's response to medications can change, making some drugs more potent and others less effective.
- Altered Receptor Sensitivity: Older adults may have altered receptor numbers or sensitivity. For example, reduced sensitivity in cardiac $\beta$-adrenergic receptors can lead to a weaker response to $\beta$-agonist drugs.
- Increased Central Nervous System (CNS) Sensitivity: Older adults are more susceptible to the CNS effects of drugs like psychotropics, benzodiazepines, and anticholinergics. This increases the risk of confusion, delirium, falls, and sedation.
- Diminished Homeostatic Mechanisms: A decline in the body's compensatory mechanisms can heighten a drug's effect. For instance, a medication that lowers blood pressure may cause more severe orthostatic hypotension (dizziness upon standing) in an older adult than in a younger person.
Comparison of Pediatric and Geriatric Medication Administration
| Feature | Pediatric (Infants and Children) | Geriatric (Older Adults) |
|---|---|---|
| Body Composition | Higher total body water, lower body fat, lower plasma protein concentrations. | Lower total body water, higher body fat, potentially lower plasma albumin. |
| Drug Dosing | Primarily based on body weight or surface area, with frequent re-evaluation as the child grows. | Start low and go slow; lower doses often required due to reduced clearance and increased sensitivity. |
| Metabolism | Immature liver enzyme systems (Phase I slower, Phase II variable) initially, with rapid maturation. | Declining liver function, reduced hepatic blood flow, and decreased Phase I metabolism. |
| Excretion | Immature renal function at birth, maturing over the first few months to years. | Declining renal function and GFR, leading to reduced drug clearance. |
| Administration | Challenges with swallowing, measuring, and adherence. Liquid formulations often preferred; use calibrated devices. | Potential difficulty with swallowing, impaired vision/memory, polypharmacy, and complex schedules. |
| Monitoring | Frequent monitoring of weight and clinical response due to rapid developmental changes. | Regular medication reviews, careful monitoring for ADRs, and adjusting for comorbidities. |
Practical Steps for Safe Medication Administration
Ensuring safe medication administration across all ages requires proactive measures from both healthcare providers and patients or caregivers.
- Accurate Dosing and Measurement: Always use weight-based calculations for children and verify dosages carefully. For liquid medications, use the calibrated measuring device provided with the medicine, not a kitchen spoon.
- Simplify Medication Regimens: For older adults, consolidating medications or adjusting schedules to fewer doses can improve adherence. Using aids like pill boxes or setting electronic reminders is also helpful.
- Maintain a Comprehensive Medication List: Keep a detailed, current list of all medications, including over-the-counter drugs, supplements, and vitamins. Share this list with every healthcare provider to prevent drug interactions.
- Engage in Medication Reviews: Regular medication reviews with a pharmacist or doctor can identify unnecessary medications (polypharmacy), ineffective treatments, and potential interactions.
- Monitor for Side Effects: Older adults, especially, are more susceptible to medication side effects. Report any new or worsening symptoms, such as dizziness, confusion, or balance issues, to a healthcare provider.
- Proper Storage and Disposal: Store medications according to instructions, away from children, pets, and environmental extremes. Regularly check expiration dates and use designated take-back programs for safe disposal.
Conclusion
Age is a critical variable that fundamentally affects medication administration, influencing everything from optimal drug dosage to the risk of side effects. While pediatric patients require dosing adjustments due to their immature organ systems and rapid development, older adults face challenges from declining physiological function, comorbidities, and the complexities of polypharmacy. By understanding these age-related changes in pharmacokinetics and pharmacodynamics, healthcare providers and patients can work together to implement safer and more effective medication management strategies. Adherence to individualized dosing, careful monitoring, and clear communication are essential for navigating the complexities of medication administration throughout the lifespan. For more information on medication safety, refer to guidelines from the U.S. Food and Drug Administration (FDA).
References
- Food and Drug Administration (FDA). "As You Age: You and Your Medicines."
- Hutchison, B. & O'Brien, P. (2007). "Pharmacokinetics in the elderly." Clinical Pharmacology & Therapeutics.
- Merck Manuals. "Overview of Drug Treatment in Children."
- National Institute on Aging (NIA). "Taking Medicines Safely as You Age."
- ScienceDirect. "Developmental Pharmacokinetics."
- HealthInAging.org. "Medications Work Differently in Older Adults."
