Dosage: How to Determine the Right Amount for Adults and Children

Dosage: How to Determine the Right Amount for Adults and ChildrenAccurate dosing is essential for medication effectiveness and safety. An appropriate dose maximizes benefit while minimizing harm. Determining the right dose requires considering the medication’s properties, the patient’s characteristics (age, weight, organ function, comorbidities), route of administration, and clinical context. This article explains principles, practical methods, common pitfalls, and special situations for dosing adults and children.

Basic principles of dosing

• Therapeutic window: Most drugs have a range between the minimum effective concentration and the concentration where toxicity occurs. The goal is to keep drug exposure within this window.
• Pharmacokinetics (PK): How the body affects the drug—absorption, distribution, metabolism, and excretion—determines dosing frequency and amount.
• Pharmacodynamics (PD): How the drug affects the body—relationship between concentration and effect—guides target concentrations.
• Individual variability: Genetics, age, weight, organ function, interactions, and adherence produce large patient-to-patient differences.

Adult dosing: common methods and considerations

1. Standard adult dosing

   • Many medications provide a fixed “standard” adult dose (e.g., metformin 500–1000 mg twice daily). These assume average body size and organ function.
   • Use standard doses for most healthy adults unless contraindications or special factors exist.

2. Weight-based dosing

   • Drugs with narrow therapeutic windows or those where distribution scales with body size (e.g., many chemotherapeutics, aminoglycoside antibiotics, some anticoagulants) often use mg/kg dosing.
   • Example calculation: for a drug dosed at 5 mg/kg in a 70 kg adult → 5 × 70 = 350 mg.

3. BSA-based dosing

   • Body surface area (BSA) dosing is common in oncology (mg/m2). BSA better correlates with metabolic mass than weight alone for some agents.
   • Mosteller formula (common): BSA (m2) = sqrt([height(cm) × weight(kg)]/3600).

4. Organ function adjustments

   • Renal impairment: many drugs or metabolites are renally cleared; dose reduction or extended dosing intervals are required. Check creatinine clearance (CrCl) or eGFR.
   • Hepatic impairment: drugs metabolized extensively by the liver may need dose reductions; guidance often provided by drug manufacturers.

5. Therapeutic drug monitoring (TDM)

   • For drugs with narrow therapeutic windows (e.g., warfarin, aminoglycosides, vancomycin, some anticonvulsants), measure drug concentrations or surrogate markers and adjust dosing accordingly.

6. Drug interactions and polypharmacy

   • CYP enzyme inducers/inhibitors, P-glycoprotein interactions, and other mechanisms can change drug levels; adjust doses when significant interactions occur.

7. Special populations in adults

   • Elderly: decreased renal function, altered body composition (higher fat, lower water), and increased sensitivity to many drugs. Start low and go slow.
   • Pregnant people: physiologic changes (increased blood volume, increased renal clearance) can alter dosing; fetal safety must be considered.

Pediatric dosing: special rules and methods

Children are not “small adults.” Their physiology changes rapidly with age, affecting absorption, distribution, metabolism, and excretion. Dosing must account for age-related differences.

1. Age groups to consider

   • Neonates (0–28 days)
   • Infants (1–12 months)
   • Toddlers and young children (1–5 years)
   • Older children and adolescents (6–17 years)

2. Weight-based dosing (mg/kg)

   • Most common pediatric approach. Always use current weight in kilograms and round doses to practical administration units.
   • Example: Amoxicillin 40 mg/kg/day divided twice daily for a 12-kg toddler → total = 480 mg/day → 240 mg every 12 hours.

3. BSA-based dosing

   • Used for certain drugs (e.g., chemotherapy) where body surface area better predicts drug handling.

4. Age- or gestational age adjustments

   • Premature infants have immature renal and hepatic function; dosing intervals are often prolonged.
   • Enzyme maturation: some drug-metabolizing enzymes are immature in neonates and infants, altering clearance.

5. Formulation and administration

   • Use liquid formulations (suspensions) for most children; ensure concentration is known (mg/mL) to calculate volume.
   • For tablets, ensure appropriate splitting or use dispersible forms; avoid unsafe compounding unless necessary.

6. Safety and caregivers

   • Provide clear dosing instructions (dose in mg and volume in mL), dosing device (oral syringe), and timing.
   • Warn about double-dosing and measuring errors.

Step-by-step approach to calculate a dose

1. Verify the indication and target drug.
2. Check recommended dosing guidelines (drug monograph, formulary, pediatric reference).
3. Determine patient-specific data:
   • Age, weight (kg), height (cm), BSA if needed, renal function (CrCl/eGFR), hepatic status, pregnancy status.
4. Choose dosing method (standard, mg/kg, mg/m2, adjusted for organ function).
5. Calculate the dose:
   • For mg/kg: Dose = dose_per_kg × patient_weight(kg).
   • For mg/m2: Dose = dose_per_m2 × BSA(m2).
6. Adjust for renal/hepatic impairment as recommended.
7. Check maximum/minimum limits and round to practical units.
8. Provide clear dosing instructions (e.g., “250 mg PO every 8 hours” or “5 mL of 80 mg/5 mL suspension twice daily”).
9. Reassess response and adverse effects; use TDM when indicated.

Practical examples

• Adult weight-based example: Dosing 2 mg/kg of a drug for a 90 kg adult → 2 × 90 = 180 mg.
• Pediatric example: Ceftriaxone 50 mg/kg IV once daily for a 15-kg child → 50 × 15 = 750 mg (round per vial availability).
• Renal adjustment example: If typical dose is 500 mg q12h but eGFR <30 mL/min recommends q24h, change timing rather than dose.

Common dosing pitfalls and how to avoid them

• Mistaken units (mg vs mL vs IU): Always confirm concentration and units.
• Using outdated weight: Weigh the patient at the visit.
• Calculation errors: Use double-checks or computerized calculators; have another clinician verify high-risk doses.
• Confusing dosing frequency: Clarify “q8h” vs “three times a day” and provide clock-based times for caregivers.
• Failure to adjust for organ dysfunction or drug interactions.

When to consult specialists

• Narrow therapeutic index drugs (e.g., chemotherapeutics, immunosuppressants, certain anticonvulsants).
• Complex renal or hepatic impairment.
• Pediatric neonates or extremely low birth weight infants.
• Drug–drug interaction concerns in polypharmacy.
• Unclear dosing recommendations from product literature.

Documentation and communication

• Document dose calculation, rationale, and any adjustments.
• Provide clear patient/caregiver instructions with dose in mg and volume (if liquid), schedule, and storage.
• Advise on missed dose actions and warning signs of toxicity or inadequate effect.

Summary

Determining the right dose combines standard recommendations with individualized factors: weight, age, organ function, route, and clinical response. Use weight- or BSA-based calculations when appropriate, adjust for renal/hepatic function, employ therapeutic drug monitoring for narrow-window drugs, and always double-check math and units. Clear communication and documentation reduce medication errors and improve outcomes.