Drug dosing in special patient populations is a critical component of clinical pharmacokinetics. Elderly patients, children, and obese individuals have significant physiological differences that influence the pharmacokinetics and pharmacodynamics of medications. Understanding these variations helps clinicians design safe and effective dosing regimens to avoid toxicity, underdosing, or treatment failure.
Introduction
Drug dosing cannot follow a “one-size-fits-all” approach. Age, body composition, and organ function have profound effects on absorption, distribution, metabolism, and excretion (ADME). Special populations require individualized therapy based on patient-specific characteristics and pharmacokinetic principles.
The three important groups discussed here include:
- Elderly patients
- Pediatric patients
- Obese patients
Drug Dosing in the Elderly
Physiological Changes in the Elderly
Aging brings several physiological changes that influence drug handling:
1. Absorption
- Reduced gastric acid secretion
- Delayed gastric emptying
- Altered intestinal motility
2. Distribution
- Increased body fat → higher Vd for lipophilic drugs
- Decreased lean body mass
- Reduced total body water → higher plasma concentration of hydrophilic drugs
- Reduced albumin → increased free fraction of highly protein-bound drugs
3. Metabolism
- Reduced hepatic blood flow
- Decreased Phase I metabolism
4. Excretion
- Decline in renal clearance (CrCl and GFR decrease with age)
Dosing Considerations for Elderly Patients
- Start low and go slow—begin with lower doses and titrate gradually
- Adjust doses for renally cleared drugs (e.g., digoxin, aminoglycosides)
- Monitor drug interactions due to polypharmacy
- Watch for increased sensitivity to CNS drugs and sedatives
- Therapeutic drug monitoring (TDM) is highly recommended
Common Risks in Elderly Dosing
- Drug accumulation due to reduced clearance
- Increased toxicity risks (e.g., anticoagulants, CNS depressants)
- Higher susceptibility to hypotension and electrolyte disturbances
Drug Dosing in Pediatric Patients
Unique Characteristics of Children
Children are not “small adults.” Pharmacokinetics undergo dramatic changes from infancy to adolescence.
1. Absorption
- Higher gastric pH in neonates → altered absorption of weak acids and bases
- Delayed gastric emptying
2. Distribution
- Higher total body water → larger Vd for hydrophilic drugs
- Lower body fat in neonates
- Lower protein binding capacity → increased free drug levels
3. Metabolism
- Immature hepatic enzymes in neonates
- Children may have increased metabolism compared to adults (age-dependent)
4. Excretion
- GFR is low in neonates but reaches adult levels by 1 year
Pediatric Dose Calculation Methods
1. Weight-Based Dosing
Dose (mg) = mg/kg × body weight
2. Body Surface Area (BSA) Dosing
Dose = (BSA/1.73 m²) × Adult dose
BSA-based dosing is common for anticancer drugs and narrow therapeutic index medications.
Dosing Considerations for Pediatric Patients
- Use age-appropriate dosage forms (syrups, drops)
- Adjust doses frequently as the child grows
- Closely monitor for toxicity due to immature metabolism
- Avoid drugs contraindicated in pediatric populations
Drug Dosing in Obese Patients
Challenges in Obesity
Obesity alters pharmacokinetics significantly due to increased body fat, altered physiology, and comorbidities such as sleep apnea, diabetes, and cardiovascular disease.
Pharmacokinetic Changes in Obesity
1. Absorption
- Minimal impact, but altered gastric emptying may occur
2. Distribution
- Increased adipose tissue → increased Vd for lipophilic drugs
- Reduced Vd for hydrophilic drugs
- Altered protein binding
3. Metabolism
- Fatty liver disease may alter drug metabolism
- Some hepatic enzymes may be upregulated
4. Excretion
- GFR may be increased initially, then decline in long-term obesity
Weight Scalars Used in Obesity Dosing
Drug dosing often uses different body weight measurements:
- Actual Body Weight (ABW)
- Ideal Body Weight (IBW)
- Adjusted Body Weight (AdjBW)
Adjusted Body Weight = IBW + 0.4 (ABW – IBW)
Hydrophilic drugs often use IBW, whereas lipophilic drugs may require ABW.
Dosing Considerations for Obese Patients
- Use appropriate weight scalar depending on drug Vd
- Watch for altered clearance and potential accumulation
- Monitor cardiovascular and renal function
- Use TDM when possible (e.g., vancomycin, aminoglycosides)
Detailed Notes:
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